EGLN2 p.Pro231=
c.693G>A · rs2545763 · VCV1273186
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 25.9%, eas) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.51 | phastCons 0.001 |
| Overall | ||
| CADD | 6.161 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
25.9%
East Asian · 11,606/44,872 alleles
Filtering AF
25.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 25.3%
Overall
5.59%
90,217/1,612,864 alleles · common
exomes 79,725/1,460,542 · genomes 10,492/152,322 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 25.9% | 4 |
| Finnishnot grpmax-eligible | 9.85% | 10 |
| African / African-American | 9.68% | 10 |
| Remaining individualsnot grpmax-eligible | 6.09% | 16 |
| Middle Eastern | 5.43% | 18 |
| Ashkenazi Jewishnot grpmax-eligible | 4.62% | 22 |
| European (non-Finnish) | 4.61% | 22 |
| South Asian | 4.11% | 24 |
| Admixed American | 2.48% | 40 |
| Amishnot grpmax-eligible | 1.1% | 91 |
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
- EGLN2
- Protein
- p.Pro231=
- Coding
- c.693G>A
- MANE Select
- NM_080732
- dbSNP
- rs2545763
- Type
- single nucleotide variant
- Location
- chr19:40801265 (GRCh38)
- Gene constraint
- LOEUF 0.582 · pLI 0.67 (gnomAD)
- Structure
- AlphaFold pLDDT 69.05 · 1 PDB
- Residue 231
- the 'beta(2)beta(3) 'finger-like' loop' region
Similar variants
- EGLN2 p.Pro231Leu Uncertain significance ★ ⚠ same residue
- EGLN2 p.Ala137Thr Uncertain significance ★★ ⚠ same type
- EGLN2 p.Arg236Cys Uncertain significance ★★ ⚠ same type
- EGLN2 p.Arg306Cys Uncertain significance ★★ ⚠ same type
- EGLN2 c.1100+23C>A Benign ★★ same type
- EGLN2 c.844-141G>A Benign ★★ same type
- EGLN2 c.844-199G>A Benign ★★ same type
- EGLN2 c.963+33G>C 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/egln2-p-pro231 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown