FOXC1 p.Pro273=
c.819C>A · rs931714808 · VCV1625269
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 9.26e-05%, nfe)
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 -0.18 | GERP -3.6, phastCons 0.011 |
| Overall | ||
| CADD | 8.288 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
9.26e-05%
European (non-Finnish) · 1/1,079,676 alleles
Overall
7.97e-05%
1/1,254,756 alleles · very rare
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.Pro273=
- Coding
- c.819C>A
- MANE Select
- NM_001453
- dbSNP
- rs931714808
- Type
- single nucleotide variant
- Location
- chr6:1611264 (GRCh38)
- Gene constraint
- LOEUF 1.276 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 56.09
- Residue 273
- the 'disordered' region; the 'required for transcriptional inhibition' region
Similar variants
- FOXC1 p.Pro273Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- FOXC1 p.Pro273Ser Uncertain significance ★ ⚠ same residue
- 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
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-pro273 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown