AKR1E2 p.Pro199=
c.597A>G · rs2290349 · VCV1264863
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 12.3%, 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 | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4 | GERP -3.8 |
| Overall | ||
| CADD | 4.296 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
12.3%
East Asian · 5,536/44,874 alleles
Filtering AF
12.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 12%
Overall
4.25%
68,559/1,613,432 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 12.3% | 8 |
| European (non-Finnish) | 4.66% | 21 |
| Remaining individualsnot grpmax-eligible | 3.65% | 27 |
| Admixed American | 3.24% | 31 |
| South Asian | 1.73% | 58 |
| Finnishnot grpmax-eligible | 1.69% | 59 |
| Ashkenazi Jewishnot grpmax-eligible | 1.52% | 66 |
| Middle Eastern | 1.35% | 74 |
| African / African-American | 0.864% | 116 |
| Amishnot grpmax-eligible | 0.11% | 912 |
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
- AKR1E2
- Protein
- p.Pro199=
- Coding
- c.597A>G
- MANE Select
- NM_001040177
- dbSNP
- rs2290349
- Type
- single nucleotide variant
- Location
- chr10:4839743 (GRCh38)
- Gene constraint
- LOEUF 1.302 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.51
Similar variants
- AKR1E2 c.207+72T>C Benign ★★ same type
- AKR1E2 c.208-87C>T Benign ★★ same type
- AKR1E2 c.324+6G>A Benign ★★ same type
- AKR1E2 c.325-48G>T Likely benign ★★ same type
- AKR1E2 c.325-50T>G Likely benign ★★ same type
- AKR1E2 c.39+10T>C Benign ★★ same type
- AKR1E2 c.40-180T>G Benign ★★ same type
- AKR1E2 c.40-98T>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/akr1e2-p-pro199 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown