Is EPM2A p.Arg91Trp (c.271C>T) pathogenic?

EPM2A p.Arg91Trp (c.271C>T) is classified Uncertain significance in EPM2A (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-23). Very rare (popmax 0.00241%, sas); Associated with progressive myoclonus epilepsy.

What condition is associated with EPM2A p.Arg91Trp (c.271C>T)?

EPM2A p.Arg91Trp (c.271C>T) is associated with progressive myoclonus epilepsy (ClinVar).

How common is EPM2A p.Arg91Trp (c.271C>T) in the general population?

EPM2A p.Arg91Trp (c.271C>T) is very rare (popmax 0.00241%, sas) (gnomAD).

EPM2A p.Arg91Trp

c.271C>T · rs752244019 · VCV947752

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00241%, sas)

Conditions

progressive myoclonus epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.684	pathogenic-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.7	GERP -1.4, phastCons 0.97
Regional constraint	o/e 1.04	unconstrained · MANE · 108 kb · p 0.41 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00241% South Asian · 2/83,042 alleles

Filtering AF 0.0004% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00015%

Overall 0.000216% 3/1,385,918 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00241%	41,521
European (non-Finnish)	8.76e-05%	1,141,082

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: EPM2A
Protein: p.Arg91Trp
Coding: c.271C>T
dbSNP: rs752244019
Type: single nucleotide variant
Location: chr6:145735228 (GRCh38)

Full EPM2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

progressive myoclonus epilepsy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/epm2a-p-arg91trp (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown