FOXE3 p.Pro59=
c.177G>C · rs1225970688 · VCV2150244
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00763%, 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 -0.9 | GERP -3.1 |
| Overall | ||
| CADD | 4.048 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00763%
East Asian · 2/26,200 alleles
Filtering AF
0.00126%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000472%
Overall
0.000412%
5/1,214,208 alleles · very rare
exomes 4/1,068,702 · genomes 1/145,506 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00763% | 13,100 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00624% | 16,034 |
| European (non-Finnish) | 0.000206% | 485,286 |
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.Pro59=
- Coding
- c.177G>C
- MANE Select
- NM_012186
- dbSNP
- rs1225970688
- Type
- single nucleotide variant
- Location
- chr1:47416492 (GRCh38)
- Gene constraint
- LOEUF 1.935 · pLI 0.12 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 66.68
- Residue 59
- the 'disordered' region
Similar variants
- FOXE3 p.Pro59Gln Uncertain significance ★★ ⚠ same residue
- FOXE3 p.Pro59Arg Uncertain significance ★ ⚠ same residue
- FOXE3 p.Pro59Leu 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
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-pro59 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown