FOXC1 p.Val310=
c.930G>A · rs2480504789 · VCV1950500
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000454%, 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 8.7 | GERP -3, phastCons 1 |
| Overall | ||
| CADD | 14.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000454%
European (non-Finnish) · 5/1,101,794 alleles
Filtering AF
0.000133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9.7e-05%
Overall
0.000345%
5/1,447,540 alleles · very rare
exomes 5/1,296,886 · genomes 0/150,654 · joint denominator
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.Val310=
- Coding
- c.930G>A
- MANE Select
- NM_001453
- dbSNP
- rs2480504789
- Type
- single nucleotide variant
- Location
- chr6:1611375 (GRCh38)
- Gene constraint
- LOEUF 1.276 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 56.09
- Residue 310
- 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-val310 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown