Ensembl Variation - Phenotype and disease annotations

Phenotypes are imported from a number of external sources and displayed in Ensembl. On top of these, for human we display the clinical significance of variants, and map phenotype terms using ontologies.

Clinical significance

See below the list of the clinical significance terms you can find in the human Ensembl Variation database:

IconValueClinVar exampleDGVa example
drug responsers6025nsv1197529
likely benignrs77776214nsv529995
likely pathogenicrs6122esv1791726
not providedrs4625nsv984836
risk factorrs333nsv513775
uncertain significancers184999645esv2830426

Further explanations about the clinical significance terms are available on the ClinVar website.

ClinVar rating

We use the ClinVar "four-star" rating system to indicate the quality of classification/validation of the variant:

greygreygreygrey not classified by submitter rs730882195
goldgreygreygrey classified by single submitter rs1131692257
goldgoldgreygrey classified by multiple submitters rs386833436
goldgoldgoldgrey reviewed by expert panel rs1554409395
goldgoldgoldgold practice guideline rs370803989

Phenotype/disease ontologies

We import ontology terms related to phenotypes, traits and diseases from a variety of sources using an automated process. Ontologies used are:

CMO Clinical Measurement Ontology 07-12-2018
EFO Experimental Factor Ontology 3.10.0
HPO Human Phenotype Ontology 2019-09-06
MP Mammalian Phenotype Ontology 04-09-2019
VT Vertebrate Trait Ontology 07-06-2019

Descriptions are linked to ontology terms using:

  • Mappings provided by association data sources such as Orphanet, the NHGRI-EBI GWAS catalog and ClinVar
  • Annotations of OMIM terms created by HPO
  • Annotations of OMIM terms created by Orphanet
  • Ontology LookUp Service searches of full or truncated descriptions for exact matches to terms or synomyms
  • Zooma searches of annotations curated by the European Variation Archive team

Phenotype classes

We group phenotype terms into the classes below:

Classes Example phenotypesExample variants
trait 'Hepatocellular carcinoma' from ClinVar rs11554290
tumour 'Skin tumour' from COSMIC COSV99082046
non_specified 'not specified' from ClinVar rs757730609

These can be used to retrieve corresponding subsets of phenotype annotations for genes or in a specific region via the REST API. Phenotype pages are displayed for all classes except 'non_specified' class.


  • Sebastian Köhler, Sandra C Doelken, Christopher J. Mungall, Sebastian Bauer, Helen V. Firth, Isabelle Bailleul-Forestier, Graeme C. M. Black, Danielle L. Brown, Michael Brudno, Jennifer Campbell, David R. FitzPatrick, Janan T. Eppig, Andrew P. Jackson, Kathleen Freson, Marta Girdea, Ingo Helbig, Jane A. Hurst, Johanna Jähn, Laird G. Jackson, Anne M. Kelly, David H. Ledbetter, Sahar Mansour, Christa L. Martin, Celia Moss, Andrew Mumford, Willem H. Ouwehand, Soo-Mi Park, Erin Rooney Riggs, Richard H. Scott, Sanjay Sisodiya, Steven Van Vooren, Ronald J. Wapner, Andrew O. M. Wilkie, Caroline F. Wright, Anneke T. Vulto-van Silfhout, Nicole de Leeuw, Bert B. A. de Vries, Nicole L. Washingthon, Cynthia L. Smith, Monte Westerfield, Paul Schofield, Barbara J. Ruef, Georgios V. Gkoutos, Melissa Haendel, Damian Smedley, Suzanna E. Lewis, and Peter N. Robinson
    The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data
    Nucl. Acids Res. (1 January 2014) 42 (D1): D966-D974

  • Malone J, Holloway E, Adamusiak T, Kapushesky M, Zheng J, Kolesnikov N, Zhukova, A, Brazma A, Parkinson H.
    Modeling sample variables with an Experimental Factor Ontology
    Bioinformatics (2010) 26 (8): 1112-1118