FOXC1 p.Phe533=
c.1599C>T · rs201266312 · VCV3043884
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00446%, eas)
Conditions
1
FOXC1-related disorder
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 0.1 | GERP 0.56, phastCons 0.95 |
| Overall | ||
| CADD | 7.057 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,882 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000494%
Overall
0.000372%
6/1,613,848 alleles · very rare
exomes 2/1,461,544 · genomes 4/152,304 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00446% | 22,441 |
| African / African-American | 0.004% | 25,016 |
| South Asian | 0.0011% | 91,084 |
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.Phe533=
- Coding
- c.1599C>T
- MANE Select
- NM_001453
- dbSNP
- rs201266312
- Type
- single nucleotide variant
- Location
- chr6:1612044 (GRCh38)
- Gene constraint
- LOEUF 1.276 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 56.09
- Residue 533
- the 'required for transcriptional activation' region
Disease context
FOXC1-related disorder
Similar variants
- FOXC1 p.Arg127His Pathogenic ★★ same condition
- FOXC1 p.Cys135Tyr Likely pathogenic ★★ same condition
- FOXC1 p.Gln106Ter Pathogenic ★★ same condition
- FOXC1 p.Ser131Leu Pathogenic/Likely pathogenic ★★ same condition
- FOXC1 p.Ser82Thr Pathogenic/Likely pathogenic ★★ same condition
- FOXC1 p.Phe533fs Uncertain significance ★★ same residue
- FOXC1 p.Thr437Ala Uncertain significance ★★ ⚠ same condition
- FOXC1 p.Arg169Trp Likely 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-phe533 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown