FOXE3 p.Ala45=
c.135G>A · rs886044273 · VCV1546796
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.11%, eas)
Conditions
2
anterior segment dysgenesis
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 -0.95 | GERP -3.5 |
| Overall | ||
| CADD | 5.708 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.11%
East Asian · 23/20,824 alleles
Filtering AF
0.0754%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0639%
Overall
0.00242%
27/1,116,518 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.11% | 905 |
| Remaining individualsnot grpmax-eligible | 0.0106% | 9,430 |
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.Ala45=
- Coding
- c.135G>A
- MANE Select
- NM_012186
- dbSNP
- rs886044273
- Type
- single nucleotide variant
- Location
- chr1:47416450 (GRCh38)
- Gene constraint
- LOEUF 1.935 · pLI 0.12 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 66.68
- Residue 45
- the 'disordered' region
Similar variants
- FOXE3 p.Ala45Glu Uncertain significance ★★ ⚠ same residue
- FOXE3 p.Ala45Thr 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
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-ala45 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown