Is EPM2A p.Arg312fs (c.934dup) pathogenic?

EPM2A p.Arg312fs (c.934dup) is classified Pathogenic in EPM2A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-30). Ultra-rare (gnomAD MAF 8.394e-06); Associated with progressive myoclonus epilepsy.

What condition is associated with EPM2A p.Arg312fs (c.934dup)?

EPM2A p.Arg312fs (c.934dup) is associated with progressive myoclonus epilepsy (ClinVar).

How common is EPM2A p.Arg312fs (c.934dup) in the general population?

EPM2A p.Arg312fs (c.934dup) is ultra-rare (gnomAD MAF 8.394e-06) (gnomAD).

EPM2A p.Arg312fs

c.934dup · rs2128555980 · VCV1454028

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 8.394e-06)

Conditions

progressive myoclonus epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (4 of 4) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.93	GERP -3.9

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

Global frequency 0.000839% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: EPM2A
Protein: p.Arg312fs
Coding: c.934dup
MANE Select: NM_005670
dbSNP: rs2128555980
Type: Duplication
Location: chr6:145627477 (GRCh38)
Gene constraint: LOEUF 1.191 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 34.25 · 2 PDB
Residue 312: 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.Arg312Trp Uncertain significance ★★ same residue
EPM2A p.Arg312Gln Uncertain significance ★ same residue
EPM2A p.Arg312= Likely benign ★ same residue
EPM2A p.Tyr157fs Pathogenic ★★ same condition
EPM2A p.Glu308fs Pathogenic ★ same condition
EPM2A p.Ala71_Ala72insGluLeuAlaAlaGluGluAla Uncertain significance ★ same condition
EPM2A p.Ala71_Glu77dup Uncertain significance ★ same condition
EPM2A p.Val38_Ala51dup Uncertain significance ★ 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-arg312fs (accessed [today's date]).

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