Variant Effect Predictor Download and install


Download ensembl-vep package (see below the different ways to download it) and then follow the installation instructions.

Using Git

Clone the Git repository

Use git to download the ensembl-vep package:

git clone
cd ensembl-vep

Update to a newer version

To update from a previous version:

cd ensembl-vep
git pull
git checkout release/112

Use an older version

To use an older version (this example shows how to set up release 87):

cd ensembl-vep
git checkout release/87

Download the Zipped package file

Users without the git utility installed may download a zip file from GitHub, though we would always recommend using git if possible.

curl -L -O
cd ensembl-vep-release-112/

Previous versions (ensembl-tools)

Previously VEP was available as part of the ensembl-tools package (see the Ensembl archive site for documentation). The following downloads are available for archival purposes. Show versions

What's new?

New in version 112 (May 2024)

  • Enhanced Structural Variant Support:
    • Added support for CNV:TR
    • Enabled the use of chromosome synonyms in breakends
    • Report consequences for each breakend and enable the input of single breakends
  • New plugins (supported on CLI, Web and REST):
    • AlphaMissense - annotates missense variants with the pre-computed AlphaMissense pathogenicity scores. AlphaMissense is a deep learning model developed by Google DeepMind that predicts the pathogenicity of single nucleotide missense variants.
  • New plugins (supported on CLI and Web):
    • RiboseqORFs - uses a standardized catalog of human Ribo-seq ORFs to re-calculate consequences for variants located in these translated regions
  • New plugins (supported on CLI):
    • Paralogues - fetches variants overlapping the genomic coordinates of amino acids aligned between paralogue proteins
    • AVADA - Automatic VAriant evidence DAtabase is a novel machine learning tool that uses natural language processing to automatically identify pathogenic genetic variant evidence in full-text primary literature about monogenic disease and convert it to genomic coordinates
    • GeneBe - A plugin kindly contributed by the GeneBe team, it retrieves automatic ACMG variant classification data from
    • PhenotypeOrthologous A VEP plugin that retrieves phenotype information associated with orthologous genes from model organisms
  • Plugin support added to REST and Web for:

Previous version history - from version 88: Show

Older versions (ensembl-tools) - until version 87: Show


VEP requires:
  • gcc, g++ and make
  • Perl version 5.10 or above recommended (tested on 5.10, 5.14, 5.18, 5.22, 5.26)
  • Perl packages: See this guide for more information on how to install perl modules.
    Additional libraries can be installed for extra features and enhancements but they are not required to run VEP in most of the use cases.

VEP's script will install required components of Ensembl API for you, but VEP may also be used with any pre-existing API installations you have, provided their versions match the version of VEP you are using.

VEP has been developed for UNIX-like environments and works well on Linux (e.g. Ubuntu, Debian, Mint) and Mac OSX.
It can also be used on Windows systems with a more involved installation process.


VEP's makes it easy to set up your environment for using the VEP. It will download and configure a minimal set of the Ensembl API for use by the VEP, and can also download cache files, FASTA files and plugins.

Run the following, and follow any prompts as they appear:


Additional non-essential components and enhancements must be installed manually.

Software components installed

If you already have the latest version of the API installed you do not need to run the installer, although it can be used to simply update your API version (with post-release patches applied), and retrieve cache and FASTA files. The installer downloads the API within the VEP directory and will not affect any other Ensembl API installations.

The script will also attempt to install a Perl::XS module, Bio::DB::HTS, for rapid access to bgzipped FASTA files. If this fails, you may add the --NO_HTSLIB flag when running the installer; VEP will fall back to using Bio::DB::Fasta for this functionality (more details).

Running the installer

The installer is run on the command line as follows:

 perl [options] 

Follow on-screen prompts and note warnings of any files which will be deleted/overwritten

You should not need to add any options, but configuration of the installer is possible with the flags below. Options can also be set by exporting environment variables prefixed with VEP_ before running the installer (for instance, export VEP_NO_HTSLIB=1 and export VEP_DIR_PLUGINS="/plugins").

Flag Alternate Description
Assembly version to use when using --AUTO. Most species have only one assembly available on each software release; currently this is only required for human on release 76 onwards.
Run installer without prompts. Use the following options to specify parts to install:
  • a (API + Bio::DB::HTS/htslib)
  • l (Bio::DB::HTS/htslib only)
  • c (cache)
  • f (FASTA)
  • p (plugins) — Require the use of the --PLUGINS flag to list the plugin(s) to install.

e.g. for API and cache:

perl --AUTO ac
--CACHE_VERSION [version]
  By default the installer will download the latest version of VEP caches and FASTA files (currently 112). You can force the script to install a different version, but there is no guarantee that a version of the API will be compatible with a different version of the cache.
--CACHEDIR [dir]

By default the script will install the cache files in the ".vep" subdirectory in your home area. This option configures where cache files are installed.

The --dir_cache flag must be passed when running the VEP if a non-default cache directory is given:

./vep --dir_cache [dir]
--DESTDIR [dir]

By default the script will install the API modules in a subdirectory of the current directory named "Bio". Using this option you can configure where the Bio directory is created. If something other than the default is used, this directory must either be added to your PERL5LIB environment variable when running the VEP, or included using perl's -I flag:

perl -I [dir] vep
Don't attempt to install Bio::DB::HTS/htslib
  Don't run API tests - useful if you know a harmless failure will prevent continuation of the installer
By default the script will check for new versions or updates of the VEP. Using this option will skip this check.

Comma-separated list of plugins to install when using --AUTO. To install all available plugins, use --PLUGINS all.

# List the available plugins:
perl -a p --PLUGINS list
# Download/install all the available plugins:
perl -a p --PLUGINS all
# Download/install a defined list of plugins, e.g.:
perl -a p --PLUGINS dbNSFP,CADD,G2P

By default the script will install the plugins files in the "Plugins" subdirectory of the --CACHEDIR directory. This option configures where the plugins files are installed.

The --dir_plugins flag must be passed when running the VEP if a non-default plugins directory is given:

./vep --dir_plugins [dir]
Use this if the installer fails with out of memory errors.

Comma-separated list of species to install when using --AUTO. To install the RefSeq cache, add "_refseq" to the species name, e.g. "homo_sapiens_refseq", or "_merged" to install the merged Ensembl/RefSeq cache. Remember to use --refseq or --merged when running the VEP with the relevant cache!

Use all to install data for all available species.

Don't write any status output when using --AUTO.

Additional components will set up the minimum requirements for VEP. Some features and enhancements, however, require the installation of additional components. Most are perl modules that are easily installed using cpanm; see this guide for more information on how to install perl modules.

Typically, you will use cpanm to install modules locally in your home directories; this shows how to set up a path for perl modules and install one there:

mkdir -p $HOME/cpanm
export PERL5LIB=$PERL5LIB:$HOME/cpanm/lib/perl5
cpanm -l $HOME/cpanm Set::IntervalTree

To make the change to PERL5LIB permanent, it is recommended to add the export line to your $HOME/.bashrc or $HOME/.profile.


In order for VEP to be able to access bigWig format custom annotation files, the Bio::DB::BigFile perl module is required. Installation involves downloading and compiling the kent source tree. The current version of the kent source tree does not work correctly with Bio::DB::BigFile, so it is necessary to install an archive version known to work (v335).

  1. Download and unpack the kent source tree

    tar xzf v335_base.tar.gz
  2. Set up some environment variables; these are required only temporarily for this installation process

    export KENT_SRC=$PWD/kent-335_base/src
    export MACHTYPE=$(uname -m)
    export CFLAGS="-fPIC"
    export MYSQLINC=`mysql_config --include | sed -e 's/^-I//g'`
    export MYSQLLIBS=`mysql_config --libs`
  3. Modify kent build parameters

    cd $KENT_SRC/lib
    echo 'CFLAGS="-fPIC"' > ../inc/
  4. Build kent source

    make clean && make
    cd ../jkOwnLib
    make clean && make

    If either of these steps fail, you may have some missing dependencies. Known common missing dependencies are libpng and libssl; these may be installed, for example, with apt-get on Ubuntu. If you do not have sudo access you may have to ask your sysadmin to install any missing dependencies.

    sudo apt-get install libpng-dev libssl-dev

    On Mac OSX you may use brew; the openssl libraries also need to be symbolically linked to a different path:

    brew install libpng openssl
    cd /usr/local/include
    ln -s ../opt/openssl/include/openssl .
    cd -
  5. On some systems (e.g. Mac OSX), a compiled file is placed in a path that Bio::DB::BigFile cannot find. You can correct this with:

    ln -s $KENT_SRC/lib/x86_64/* $KENT_SRC/lib/
  6. We'll now use cpanm to install the perl module for Bio::DB::BigFile itself. See above for guidance on this. In this example we're going to install the module to a path within your home directory. In order to do this we must modify the paths that perl looks in to find modules by adding to the PERL5LIB environment module. To make this change permanent you must add the export line to your $HOME/.bashrc or $HOME/.profile.

    mkdir -p $HOME/cpanm
    export PERL5LIB=$PERL5LIB:$HOME/cpanm/lib/perl5
    cpanm -l $HOME/cpanm Bio::DB::BigFile

    If you are prompted for the path to the kent source tree, that means something didn't go right in the compilation above. Double check that $KENT_SRC/lib/jkweb.a exists and is not found instead at e.g. $KENT_SRC/lib/x86_64/jkweb.a. You may copy or link the file (and the other files in that directory) to the former path.

    ln -s $KENT_SRC/lib/x86_64/* $KENT_SRC/lib/
  7. You should now be able to successfully run the appropriate test in the VEP package:

    perl -Imodules t/AnnotationSource_File_BigWig.t

Using VEP in Mac OS

Installing VEP on Mac OS is slightly trickier than other Linux-based systems, and will require additional dependancies.
These instructions will guide you through the setup of Perlbrew, Homebrew, MySQL and other dependancies that will allow for a clean installation of VEP on your Mac OS system.

These instructions have been tested on macOS High Sierra (10.13) and macOS Sierra (10.12).
Older versions may require additional tweaks, however we shall endeavor to keep these instructions up to date for future versions of MacOS.

Prerequisite Setup

List of prerequisites: XCode, GCC, Perlbrew, Cpanm, Homebrew, mysql, DBI, DBD::mysql (version <=4.050)

XCode and GCC

VEP requires XCode and GCC for installation purposes. Fortunately, recent versions of macOS will look for (and attempt to install if required) both of these when you run the following command:

gcc -v


We recommend using Perlbrew to install a new version of Perl on your mac, to prevent messing with the vendor perl too much. This can be done with the following command:

curl -L | bash

echo 'source $HOME/perl5/perlbrew/etc/bashrc' >> ~/.bash_profile

At this point, PLEASE RESTART YOUR TERMINAL WINDOW to allow for the perlbrew changes to take effect.

We recommend installing Perl version 5.26.2 to run VEP, and installing cpanm to handle the installation of perl modules.
These steps can be completed with the commands:

perlbrew install -j 5 --as 5.26.2 --thread --64all -Duseshrplib perl-5.26.2 --notest
perlbrew switch 5.26.2
perlbrew install-cpanm


This package management system for Mac OS would make the installation of the next prerequisite (i.e. xs) easier.

/usr/bin/ruby -e "$(curl -fsSL"


VEP requires the installation of xz, a data-compression utility. The easiest way to install the xz package is through homebrew:

brew install xz


In order to connect to the Ensembl databases, a collection of MySQL related dependancies are required. Fortunately, these can be installed neatly with Homebrew and Cpanm:

brew install mysql
cpanm DBI
cpanm DBD::mysql@4.050

Installing BioPerl

On some versions of macOS, the VEP installer fails to cleanly install BioPerl, so a manual install will prevent issues:

curl -O
tar zxvf BioPerl-1.6.924.tar.gz
echo 'export PERL5LIB=${PERL5LIB}:##PATH_TO##/bioperl-1.6.924' >> ~/.bash_profile

where ##PATH_TO##/bioperl-1.6.924 refers to the location of the newly unzipped BioPerl directory.

Final Dependancies

Installing the following Perl modules with cpanm will allow for full VEP functionality:

cpanm Test::Differences Test::Exception Test::Perl::Critic Archive::Zip PadWalker Error Devel::Cycle Role::Tiny::With Module::Build

export DYLD_LIBRARY_PATH=/usr/local/mysql/lib/:$DYLD_LIBRARY_PATH

Installing VEP

And that should be that! You should now be able to install VEP using the installer:

git clone
cd ensembl-vep
perl --NO_TEST

Using VEP in Windows

VEP was developed as a command-line tool, and as a Perl script its natural environment is a Linux system. However, there are several ways you can use VEP on a Windows machine.

You may also consider using VEP's web or REST interfaces.

Virtual machines

Using a virtual machine you can run a virtual Linux system in a window on your machine. There are two ways to do this:

  1. Use the Ensembl virtual machine image
  2. Use Docker


If Perl is installed on Windows, VEP can be setup. However this may require installation of dependent modules. We recommend using Docker to run VEP on Windows.

  1. Check Perl is installed
  2. Download and unpack the zip of the ensembl-vep package
  3. Open a Command Prompt (search for Command Prompt in the Start Menu)
  4. Navigate to the directory where you unpacked the VEP package, e.g.

    cd Downloads/ensembl-vep-release-112
  5. Run with --NO_HTSLIB and --NO_TEST; you will see some warnings about the "which" command not being available (these will also appear when running VEP and can be ignored).

    perl --NO_HTSLIB --NO_TEST


Docker allows running applications in virtualised containers. The VEP Docker image is available from DockerHub: VEP in DockerHub

After installing Docker, download the VEP Docker image:

docker pull ensemblorg/ensembl-vep

To download cache files and other data with VEP Docker, we recommend mounting a directory from your local (host) machine to folder /data from the Docker image. For instance:

mkdir $HOME/vep_data
docker run -t -i -v $HOME/vep_data:/data ensemblorg/ensembl-vep

In the example above, data in $HOME/vep_data will be accessible by both the local machine and VEP Docker. The Ensembl VEP API, plugins and their dependencies (e.g. Perl APIs, Bio::DB::HTS, htslib, ...) are already installed in the image.

Read/Write access from the container

In some distributions (e.g. CentOS, Fedora, Red Hat Enterprise Linux) Docker daemon requires root privileges (i.e. needs to prefix the command with sudo), which might cause read/write issues to the mounted volume.

One solution is to use the option :Z within the Docker -v option (only from docker 1.7.0):

sudo docker run -t -i -v $HOME/vep_data:/data:Z ensemblorg/ensembl-vep

An other solution is to change the read/write access of the mounted volume ($HOME/vep_data):

chmod -R a+rwx $HOME/vep_data

Cache and FASTA files installation

You can run the script to install the cache and FASTA files:

docker run -t -i -v $HOME/vep_data:/data ensemblorg/ensembl-vep
  • You will be asked to install cache data. Type the comma-separated numbers for the species/assembly of interest and press enter. Your data will download and unpack; this may take a while.
  • If you wish to retrieve HGVS annotations, please download the FASTA files for your species. To do this, at the next prompt type 0 and press enter.

The above process may also be performed in one command; for example, to set up the cache and corresponding FASTA for human GRCh38:

docker run -t -i -v $HOME/vep_data:/data ensemblorg/ensembl-vep -a cf -s homo_sapiens -y GRCh38

The installer downloads VEP data to the mounted directory (e.g., $HOME/vep_data). The downloaded data will be automatically detected as long as its folder is mounted when running VEP:

docker run -v $HOME/vep_data:/data ensemblorg/ensembl-vep vep -i examples/homo_sapiens_GRCh38.vcf --cache

Running VEP with data from local folder

Here is an example on running VEP with data from folder $HOME/vep_data in the local machine (provided that the cache has been downloaded to that folder):

docker run -v $HOME/vep_data:/data ensemblorg/ensembl-vep \
  vep --cache --offline --format vcf --vcf --force_overwrite \
      --input_file input/my_input.vcf \
      --output_file output/my_output.vcf \
      --custom file=custom/my_extra_data.bed,short_name=BED_DATA,format=bed,type=exact,coords=1 \
      --plugin NMD

Please avoid using absolute paths to data as the paths inside the container differ from your local machine.

Update from a previous version

  1. Update your Docker container

    docker pull ensemblorg/ensembl-vep
  2. Update your cache

    # Install the new cache through the VEP script (see "Cache installation" section above)
    docker run -t -i -v $HOME/vep_data:/data ensemblorg/ensembl-vep -a c
    # Or install the cache manually
    cd $HOME/vep_data
    curl -O
    tar xzf homo_sapiens_vep_112_GRCh38.tar.gz


Due to root requirements for the Docker daemon, using the Docker container for VEP is not always possible to HPC users. Singularity, an alternative containerisation tool, does not assume that you have a system where you are the root user. This has led to increased popularity in HPC contexts due to increased access rights flexibility.

After installing Singularity, VEP may be used with Singularity based on the VEP Docker image from DockerHub:

singularity pull --name vep.sif docker://ensemblorg/ensembl-vep

The following is a brief example showing how to use a directory on your local (host) machine to store cache data for VEP.

mkdir $HOME/vep_data
singularity exec vep.sif vep --dir $HOME/vep_data --help

The Ensembl VEP API, plugins and their dependencies (e.g. Perl APIs, Bio::DB::HTS, htslib, ...) are already installed in the image.

Cache and FASTA files installation

You can run the script to install the Cache data and FASTA files. For example, to set up the cache and corresponding FASTA for human GRCh38 in your local folder $HOME/vep_data:

singularity exec vep.sif -c $HOME/vep_data -a cf -s homo_sapiens -y GRCh38

The installer downloads data to the specified directory (e.g., $HOME/vep_data). When running VEP via Singularity, point to this directory using --dir:

singularity exec vep.sif vep --dir $HOME/vep_data -i examples/homo_sapiens_GRCh38.vcf --cache

Running VEP with data from local folder

Here is an example on running VEP with data from folder $HOME/vep_data in the local machine (provided that the cache has been downloaded to that folder):

singularity exec vep.sif \
  vep --dir $HOME/vep_data \
      --cache --offline --format vcf --vcf --force_overwrite \
      --input_file input/my_input.vcf \
      --output_file output/my_output.vcf \
      --custom file=custom/my_extra_data.bed,short_name=BED_DATA,format=bed,type=exact,coords=1 \
      --plugin NMD

Update from a previous version

  1. Update your docker container

    singularity pull --name vep.sif docker://ensemblorg/ensembl-vep
  2. Update your cache

    # Install the new cache through the VEP script (see "Cache installation" section above)
    singularity exec vep.sif -c $HOME/vep_data -a c
    # Or install the cache manually
    cd $HOME/vep_data
    curl -O
    tar xzf homo_sapiens_vep_112_GRCh38.tar.gz