EPHX1 p.Ala433=
c.1299G>A · rs45550332 · VCV780304
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 5.42%, afr) — 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 -9.4 | GERP -2.8 |
| Overall | ||
| CADD | 0.317 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
5.42%
African / African-American · 4,063/75,000 alleles
Filtering AF
5.28%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.22%
Overall
0.307%
4,948/1,613,426 alleles · common
exomes 2,585/1,461,170 · genomes 2,363/152,256 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 5.42% | 18 |
| Remaining individualsnot grpmax-eligible | 0.479% | 209 |
| Admixed American | 0.478% | 209 |
| Middle Eastern | 0.454% | 220 |
| East Asian | 0.0691% | 1,448 |
| European (non-Finnish) | 0.0192% | 5,221 |
| South Asian | 0.0187% | 5,356 |
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
- EPHX1
- Protein
- p.Ala433=
- Coding
- c.1299G>A
- MANE Select
- NM_001136018
- dbSNP
- rs45550332
- Type
- single nucleotide variant
- Location
- chr1:225845278 (GRCh38)
- Gene constraint
- LOEUF 1.1 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 95.06
Similar variants
- EPHX1 c.1041-181G>A Benign ★★ same type
- EPHX1 c.183+20G>A Benign ★★ same type
- EPHX1 c.364+114G>C Benign ★★ same type
- EPHX1 c.365-3C>A Benign ★★ same type
- EPHX1 c.592+34G>A Benign ★★ same type
- EPHX1 c.-5-29G>A Benign ★★ same type
- EPHX1 c.-5-45G>A Benign ★★ same type
- EPHX1 c.*35A>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/ephx1-p-ala433 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown