FOXC1 p.Pro236=
c.708G>A · rs775979008 · VCV1139642
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0738%, eas)
Conditions
1
Axenfeld-Rieger syndrome type 3
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 2.9 | GERP -0.094, phastCons 1 |
| Overall | ||
| CADD | 12.83 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0738%
East Asian · 23/31,176 alleles
Filtering AF
0.0504%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0427%
Overall
0.00194%
28/1,441,174 alleles · ultra-rare
exomes 23/1,291,224 · genomes 5/149,950 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0738% | 1,355 |
| Remaining individualsnot grpmax-eligible | 0.00557% | 17,952 |
| South Asian | 0.00132% | 75,852 |
| European (non-Finnish) | 9.17e-05% | 1,090,182 |
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
- FOXC1
- Protein
- p.Pro236=
- Coding
- c.708G>A
- MANE Select
- NM_001453
- dbSNP
- rs775979008
- Type
- single nucleotide variant
- Location
- chr6:1611153 (GRCh38)
- Gene constraint
- LOEUF 1.276 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 56.09
- Residue 236
- the 'disordered' region; the 'required for transcriptional inhibition' region
Similar variants
- FOXC1 p.Arg127His Pathogenic ★★ same condition
- FOXC1 p.Arg127Leu Pathogenic/Likely pathogenic ★★ same condition
- FOXC1 p.Arg170Trp Pathogenic ★★ same condition
- FOXC1 p.Cys135Tyr Likely pathogenic ★★ same condition
- FOXC1 p.Gln106Ter Pathogenic ★★ same condition
- FOXC1 p.Gln120Ter Pathogenic ★★ same condition
- FOXC1 p.Gln70Ter Pathogenic ★★ same condition
- FOXC1 p.Gln92Ter Pathogenic ★★ 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/foxc1-p-pro236 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown