Is EPM2A p.Asp215= (c.645C>T) pathogenic?

EPM2A p.Asp215= (c.645C>T) is classified Likely benign in EPM2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-06). Absent from gnomAD v4.1; Associated with progressive myoclonus epilepsy.

What condition is associated with EPM2A p.Asp215= (c.645C>T)?

EPM2A p.Asp215= (c.645C>T) is associated with progressive myoclonus epilepsy (ClinVar).

How common is EPM2A p.Asp215= (c.645C>T) in the general population?

EPM2A p.Asp215= (c.645C>T) is absent from gnomAD v4.1 (gnomAD).

EPM2A p.Asp215=

c.645C>T · VCV4754074

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

progressive myoclonus epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.077	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 1.1, phastCons 1
Overall
CADD	9.609	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EPM2A
Protein: p.Asp215=
Coding: c.645C>T
MANE Select: NM_005670
Type: single nucleotide variant
Location: chr6:145635318 (GRCh38)
Gene constraint: LOEUF 1.191 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 34.25 · 2 PDB
Residue 215: an α-helix; the tyrosine-protein phosphatase domain

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

Similar variants

EPM2A p.Asp215Val Uncertain significance ★★ same residue
EPM2A c.301+1G>T Pathogenic ★★ same condition
EPM2A c.302-1G>C Pathogenic/Likely pathogenic ★★ same condition
EPM2A c.302-2A>G Pathogenic ★★ same condition
EPM2A p.Arg108Cys Pathogenic/Likely pathogenic ★★ same condition
EPM2A p.Arg171His Pathogenic/Likely pathogenic ★★ same condition
EPM2A p.Arg241Ter Pathogenic/Likely pathogenic ★★ same condition
EPM2A p.Gly279Cys Pathogenic/Likely pathogenic ★★ same condition

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-asp215 (accessed [today's date]).

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