FOXE3 p.Pro173=
c.519C>A · rs577539007 · VCV1570974
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00249%, nfe)
Conditions
2
anterior segment dysgenesis
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.6 | GERP -2.9 |
| Overall | ||
| CADD | 6.672 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00249%
European (non-Finnish) · 28/1,122,996 alleles
Filtering AF
0.00173%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00149%
Overall
0.00194%
29/1,493,208 alleles · very rare
exomes 29/1,342,992 · genomes 0/150,216 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00249% | 40,107 |
| Admixed American | 0.00241% | 41,438 |
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.Pro173=
- Coding
- c.519C>A
- MANE Select
- NM_012186
- dbSNP
- rs577539007
- Type
- single nucleotide variant
- Location
- chr1:47416834 (GRCh38)
- Gene constraint
- LOEUF 1.935 · pLI 0.12 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 66.68
Similar variants
- 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
- FOXE3 p.Ala214Val 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-pro173 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown