FOXC1 p.Ala486=
c.1458G>C · rs1051934 · VCV2158826
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00394%, amr)
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 -1.1 | GERP -2.1 |
| Overall | ||
| CADD | 8.948 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00394%
Admixed American · 2/50,778 alleles
Filtering AF
0.000653%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000244%
Overall
0.000647%
10/1,545,048 alleles · very rare
exomes 9/1,396,816 · genomes 1/148,232 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00394% | 25,389 |
| European (non-Finnish) | 0.000699% | 143,089 |
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.Ala486=
- Coding
- c.1458G>C
- MANE Select
- NM_001453
- dbSNP
- rs1051934
- Type
- single nucleotide variant
- Location
- chr6:1611903 (GRCh38)
- Gene constraint
- LOEUF 1.276 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 56.09
- Residue 486
- the 'required for transcriptional activation' region
Similar variants
- FOXC1 p.Ala486Pro 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
- FOXC1 p.Gln70Ter 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-ala486 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown