EPM2A p.Ala43=
c.129C>G · rs547147183 · VCV137223
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
rare (popmax 0.416%, afr)
Conditions
2
Inborn genetic diseases
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 -0.81 | GERP -1.3, phastCons 0.016 |
| Overall | ||
| CADD | 5.345 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.416%
African / African-American · 261/62,764 alleles
Filtering AF
0.374%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.358%
Overall
0.0251%
314/1,250,822 alleles · rare
exomes 117/1,101,324 · genomes 197/149,498 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.416% | 240 |
| Middle Eastern | 0.0946% | 1,057 |
| Remaining individualsnot grpmax-eligible | 0.0379% | 2,635 |
| Admixed American | 0.0378% | 2,644 |
| South Asian | 0.00259% | 38,608 |
| European (non-Finnish) | 0.0023% | 43,528 |
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.Ala43=
- Coding
- c.129C>G
- MANE Select
- NM_005670
- dbSNP
- rs547147183
- Type
- single nucleotide variant
- Location
- chr6:145735370 (GRCh38)
- Gene constraint
- LOEUF 1.191 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 34.25 · 2 PDB
- Residue 43
- the 'disordered' region; the cbm20 domain
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-ala43 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown