EPAS1 p.Pro752=
c.2256G>A · rs751814313 · VCV1788532
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00667%, amr)
Conditions
1
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 -11 | GERP -3.2 |
| Overall | ||
| CADD | 0.522 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00667%
Admixed American · 4/59,990 alleles
Filtering AF
0.00226%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00135%
Overall
0.00105%
17/1,613,410 alleles · very rare
exomes 16/1,461,202 · genomes 1/152,208 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00667% | 14,997 |
| East Asian | 0.00446% | 22,441 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,216 |
| South Asian | 0.0011% | 91,052 |
| European (non-Finnish) | 0.000678% | 147,493 |
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
- EPAS1
- Protein
- p.Pro752=
- Coding
- c.2256G>A
- MANE Select
- NM_001430
- dbSNP
- rs751814313
- Type
- single nucleotide variant
- Location
- chr2:46382058 (GRCh38)
- Gene constraint
- LOEUF 0.366 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 59.41 · 43 PDB
Similar variants
- EPAS1 p.Pro752Leu Benign/Likely benign ★★ same residue
- EPAS1 p.Pro752Gln Uncertain significance ★ ⚠ same residue
- EPAS1 p.Ala439Gly Uncertain significance ★★ ⚠ same condition
- EPAS1 p.Ala463Thr Uncertain significance ★★ ⚠ same condition
- EPAS1 p.Ala698Pro Uncertain significance ★★ ⚠ same condition
- EPAS1 p.Ala758Thr Uncertain significance ★★ ⚠ same condition
- EPAS1 p.Ala81Thr Uncertain significance ★★ ⚠ same condition
- EPAS1 p.Ala83Asp Uncertain significance ★★ ⚠ 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/epas1-p-pro752 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown