EPO p.Ala57=
c.171T>C · rs61735970 · VCV781763
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0967%, nfe)
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 -7.9 | GERP -3.5 |
| Overall | ||
| CADD | 0.026 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0967%
European (non-Finnish) · 1,141/1,179,426 alleles
Filtering AF
0.092%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0902%
Overall
0.075%
1,208/1,611,410 alleles · ultra-rare
exomes 1,154/1,459,214 · genomes 54/152,196 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0967% | 1,034 |
| Remaining individualsnot grpmax-eligible | 0.0866% | 1,155 |
| Admixed American | 0.0101% | 9,870 |
| African / African-American | 0.0067% | 14,930 |
| Finnishnot grpmax-eligible | 0.00313% | 31,997 |
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
- EPO
- Protein
- p.Ala57=
- Coding
- c.171T>C
- MANE Select
- NM_000799
- dbSNP
- rs61735970
- Type
- single nucleotide variant
- Location
- chr7:100721973 (GRCh38)
- Structure
- AlphaFold pLDDT 90.09 · 13 PDB
- Residue 57
- the ntr domain; a β-strand; a functional site (involved in metalloproteinase-binding)
Similar variants
- EPO c.14-1G>C Uncertain significance ★★ same type
- EPO c.13+10C>T Benign/Likely benign ★★ same type
- EPO c.247-66G>A Benign ★★ same type
- EPO p.Ala151= Benign ★★ same type
- EPO p.Ala87= Likely benign ★★ same type
- EPO p.Asp70Asn Likely benign ★★ same type
- EPO p.Lys79= Benign/Likely benign ★★ same type
- EPO p.Pro114Leu Benign/Likely benign ★★ same type
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/epo-p-ala57 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown