Is EPM2A p.Glu131= (c.393G>A) pathogenic?

EPM2A p.Glu131= (c.393G>A) is classified Benign/Likely benign in EPM2A (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-03). Rare (popmax 0.338%, nfe); Associated with Inborn genetic diseases.

What condition is associated with EPM2A p.Glu131= (c.393G>A)?

EPM2A p.Glu131= (c.393G>A) is associated with Inborn genetic diseases, progressive myoclonus epilepsy (ClinVar).

How common is EPM2A p.Glu131= (c.393G>A) in the general population?

EPM2A p.Glu131= (c.393G>A) is rare (popmax 0.338%, nfe) (gnomAD).

EPM2A p.Glu131=

c.393G>A · rs61758155 · VCV129004

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.338%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.187	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.76	GERP 0.21, phastCons 1
Overall
CADD	9.319	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.338% European (non-Finnish) · 3,990/1,179,716 alleles

Filtering AF 0.329% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.326%

Overall 0.298% 4,801/1,613,746 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.889%	112
European (non-Finnish)grpmax	0.338%	296
Remaining individualsnot grpmax-eligible	0.251%	398
Ashkenazi Jewishnot grpmax-eligible	0.135%	740
African / African-American	0.0387%	2,587
Admixed American	0.0267%	3,750

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu131=
Coding: c.393G>A
MANE Select: NM_005670
dbSNP: rs61758155
Type: single nucleotide variant
Location: chr6:145686205 (GRCh38)
Gene constraint: LOEUF 1.191 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 34.25 · 2 PDB
Residue 131: the 'disordered' region; an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: progressive myoclonus epilepsy

Similar variants

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
EPM2A p.Gly279Ser 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-glu131 (accessed [today's date]).

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