EPM2A p.Arg312=
c.936G>A · rs773315475 · VCV715191
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0217%, amr)
Conditions
1
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 -1.9 | GERP -1.9 |
| Overall | ||
| CADD | 2.638 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0217%
Admixed American · 13/60,030 alleles
Filtering AF
0.0127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0101%
Overall
0.000929%
15/1,614,230 alleles · ultra-rare
exomes 15/1,461,894 · genomes 0/152,336 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0217% | 4,618 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,510 |
| European (non-Finnish) | 8.47e-05% | 1,180,045 |
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.Arg312=
- Coding
- c.936G>A
- MANE Select
- NM_005670
- dbSNP
- rs773315475
- Type
- single nucleotide variant
- Location
- chr6:145627476 (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
Similar variants
- EPM2A p.Arg312Trp Uncertain significance ★★ same residue
- EPM2A p.Arg312Gln Uncertain significance ★ same residue
- EPM2A p.Arg312fs Pathogenic ★ 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
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-arg312 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown