Is EPM2A p.Asp49= (c.147C>T) pathogenic?

EPM2A p.Asp49= (c.147C>T) is classified Likely benign in EPM2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). Very rare (popmax 0.000677%, nfe); Associated with progressive myoclonus epilepsy.

What condition is associated with EPM2A p.Asp49= (c.147C>T)?

EPM2A p.Asp49= (c.147C>T) is associated with progressive myoclonus epilepsy (ClinVar).

How common is EPM2A p.Asp49= (c.147C>T) in the general population?

EPM2A p.Asp49= (c.147C>T) is very rare (popmax 0.000677%, nfe) (gnomAD).

EPM2A p.Asp49=

c.147C>T · VCV4754531

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000677%, nfe)

Conditions

progressive myoclonus epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.6	GERP -1.3
Overall
CADD	1.056	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000677% European (non-Finnish) · 7/1,033,474 alleles

Filtering AF 0.000282% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000181%

Overall 0.000531% 7/1,319,356 alleles · very rare exomes 7/1,169,588 · genomes 0/149,768 · joint denominator

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.Asp49=
Coding: c.147C>T
MANE Select: NM_005670
Type: single nucleotide variant
Location: chr6:145735352 (GRCh38)
Gene constraint: LOEUF 1.191 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 34.25 · 2 PDB
Residue 49: the cbm20 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.Asp49Asn Conflicting classifications of pathogenicity ★ same residue
EPM2A p.Asp49His 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

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-asp49 (accessed [today's date]).

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