FOXE1 p.Ala3=
c.9C>T · VCV4821407
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0127%, amr)
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 -1.1 | GERP -2.3, phastCons 0.003 |
| Overall | ||
| CADD | 10.69 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0127%
Admixed American · 3/23,712 alleles
Filtering AF
0.00489%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00445%
Overall
0.00586%
76/1,296,392 alleles · ultra-rare
exomes 66/1,144,244 · genomes 10/152,148 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0127% | 7,904 |
| Remaining individualsnot grpmax-eligible | 0.0103% | 9,682 |
| South Asian | 0.0103% | 9,733 |
| European (non-Finnish) | 0.00612% | 16,330 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00544% | 18,390 |
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
- FOXE1
- Protein
- p.Ala3=
- Coding
- c.9C>T
- MANE Select
- NM_004473
- Type
- single nucleotide variant
- Location
- chr9:97853923 (GRCh38)
- Gene constraint
- LOEUF 1.926 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 62.02
Similar variants
- FOXE1 p.Ala118Val Uncertain significance ★★ ⚠ same type
- FOXE1 p.Ala206Thr Uncertain significance ★★ ⚠ same type
- FOXE1 p.Arg51Gly Uncertain significance ★★ ⚠ same type
- FOXE1 p.Gly334Ala Uncertain significance ★★ ⚠ same type
- FOXE1 p.Leu205Val Uncertain significance ★★ ⚠ same type
- FOXE1 p.Ser294Asn Uncertain significance ★★ ⚠ same type
- FOXE1 c.-131G>C Benign ★★ same type
- FOXE1 c.-156T>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/foxe1-p-ala3 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown