EPM2A p.Pro301=
c.903G>C · rs141361861 · VCV137220
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.902%, afr)
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.255 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -11 | GERP -4.2 |
| Overall | ||
| CADD | 0.183 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.902%
African / African-American · 677/75,068 alleles
Filtering AF
0.846%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.823%
Overall
0.0478%
772/1,614,248 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.902% | 111 |
| Middle Eastern | 0.148% | 674 |
| Remaining individualsnot grpmax-eligible | 0.0752% | 1,330 |
| Admixed American | 0.055% | 1,819 |
| European (non-Finnish) | 0.000508% | 196,674 |
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.Pro301=
- Coding
- c.903G>C
- MANE Select
- NM_005670
- dbSNP
- rs141361861
- Type
- single nucleotide variant
- Location
- chr6:145627509 (GRCh38)
- Gene constraint
- LOEUF 1.191 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 34.25 · 2 PDB
- Residue 301
- the tyrosine-protein phosphatase domain; a UniProt-annotated variant site (in melf1; impairs protein stability; impairs phosphatase activity; affects glycogen binding; disrupts the interaction with ppp1r3c)
Similar variants
- EPM2A p.Pro301Leu Conflicting classifications of pathogenicity ★ same residue
- EPM2A p.Pro301Thr 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-pro301 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown