FOXE3 p.Pro266=
c.798C>G · rs905421694 · VCV2496960
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0256%, mid)
Conditions
3
Cardiovascular phenotype
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 -3.1 | GERP -3.5 |
| Overall | ||
| CADD | 5.745 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0256%
Middle Eastern · 1/3,908 alleles
Filtering AF
0.000498%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000186%
Overall
0.000285%
4/1,401,730 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0256% | 3,908 |
| East Asian | 0.00325% | 30,784 |
| African / African-American | 0.003% | 33,306 |
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
- FOXE3
- Protein
- p.Pro266=
- Coding
- c.798C>G
- MANE Select
- NM_012186
- dbSNP
- rs905421694
- Type
- single nucleotide variant
- Location
- chr1:47417113 (GRCh38)
- Gene constraint
- LOEUF 1.935 · pLI 0.12 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 66.68
Similar variants
- FOXE3 p.Pro266Ser Uncertain significance ★★ ⚠ same residue
- FOXE3 p.Ala78Thr Pathogenic/Likely pathogenic ★★ same condition
- FOXE3 p.Cys240Ter Pathogenic ★★ same condition
- FOXE3 p.Gly49Ter Pathogenic/Likely pathogenic ★★ same condition
- FOXE3 p.Ser211Ter Pathogenic/Likely pathogenic ★★ same condition
- FOXE3 p.Ala170Thr Uncertain significance ★★ ⚠ same condition
- FOXE3 p.Ala189Val Uncertain significance ★★ ⚠ same condition
- FOXE3 p.Ala206Asp 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/foxe3-p-pro266 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown