FOXE3 p.Ala95Pro
c.283G>C · VCV3381653
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.8206 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/2 damaging
AlphaMissense, SaProt · REVEL no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.8206 | likely pathogenic |
|---|---|---|
| REVEL | 0.571 | indeterminate |
| SaProt | LLR -9.41 | tolerated |
| ⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.5 | GERP -3.6, phastCons 1 |
| Regional constraint | o/e 1.02 | unconstrained · MANE · 956 bp · p 0.59 · regional, not allelic |
| Overall | ||
| CADD | 25.6 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- FOXE3
- Protein
- p.Ala95Pro
- Coding
- c.283G>C
- MANE Select
- NM_012186
- Type
- single nucleotide variant
- Location
- chr1:47416598 (GRCh38)
- Gene constraint
- LOEUF 1.935 · pLI 0.12 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 66.68
- Residue 95
- a DNA-binding region
Similar variants
- FOXE3 p.Ala95= Likely benign ★ same residue
- FOXE3 p.Ala78Thr Pathogenic/Likely pathogenic ★★ same type
- FOXE3 p.Cys240Ter Pathogenic ★★ same type
- FOXE3 p.Gly49Ter Pathogenic/Likely pathogenic ★★ same type
- FOXE3 p.Ser211Ter Pathogenic/Likely pathogenic ★★ same type
- FOXE3 p.Ala170Thr Uncertain significance ★★ ⚠ same type
- FOXE3 p.Ala189Val Uncertain significance ★★ ⚠ same type
- FOXE3 p.Ala206Asp Uncertain significance ★★ ⚠ 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/foxe3-p-ala95pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown