EPM2A p.Ala76Pro
c.226G>C · rs1333556119 · VCV943699
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000177%, nfe)
Conditions
1
progressive myoclonus epilepsy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.56 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not looked up on this page · why |
| Constraint at this position | ||
| Conservation | phyloP 3.8 | GERP 0.77, phastCons 1 |
| Regional constraint | o/e 1.04 | unconstrained · MANE · 108 kb · p 0.41 · regional, not allelic |
| Overall | ||
| CADD | 21.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000177%
European (non-Finnish) · 2/1,127,364 alleles
Filtering AF
3e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000147%
2/1,357,832 alleles · very rare
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.Ala76Pro
- Coding
- c.226G>C
- dbSNP
- rs1333556119
- Type
- single nucleotide variant
- Location
- chr6:145735273 (GRCh38)
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-ala76pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown