FOXC2 p.Ala207=
c.621C>G · VCV3712847
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0181%, afr)
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 -0.4 | GERP -2.8, phastCons 0.001 |
| Overall | ||
| CADD | 11.97 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0181%
African / African-American · 13/71,952 alleles
Filtering AF
0.0106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00843%
Overall
0.00103%
16/1,547,234 alleles · ultra-rare
exomes 8/1,395,140 · genomes 8/152,094 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0181% | 5,535 |
| Remaining individualsnot grpmax-eligible | 0.00167% | 59,706 |
| European (non-Finnish) | 0.000172% | 580,707 |
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
- FOXC2
- Protein
- p.Ala207=
- Coding
- c.621C>G
- MANE Select
- NM_005251
- Type
- single nucleotide variant
- Location
- chr16:86567956 (GRCh38)
- Gene constraint
- LOEUF 1.807 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 56.45 · 8 PDB
- Residue 207
- the 'disordered' region
Similar variants
- FOXC2 p.Arg121Cys Pathogenic/Likely pathogenic ★★ same type
- FOXC2 p.Gln100Ter Pathogenic ★★ same type
- FOXC2 p.Leu124Phe Likely pathogenic ★★ same type
- FOXC2 p.Tyr99Ter Pathogenic/Likely pathogenic ★★ same type
- FOXC2 p.Ala194Ser Uncertain significance ★★ ⚠ same type
- FOXC2 p.Ala326Gly Uncertain significance ★★ ⚠ same type
- FOXC2 p.Gln238Lys Uncertain significance ★★ ⚠ same type
- FOXC2 p.Gly295Ser Uncertain significance ★★ ⚠ same type
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/foxc2-p-ala207 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown