FOXC2 p.Pro248=
c.744C>T · rs375784716 · VCV2076588
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.144%, eas)
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 -2.4 | GERP -4.1 |
| Overall | ||
| CADD | 10.68 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.144%
East Asian · 49/34,088 alleles
Filtering AF
0.112%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.1%
Overall
0.0063%
89/1,412,700 alleles · rare
exomes 73/1,260,814 · genomes 16/151,886 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.144% | 696 |
| South Asian | 0.0526% | 1,902 |
| Middle Eastern | 0.0228% | 4,378 |
| Remaining individualsnot grpmax-eligible | 0.00556% | 17,995 |
| Admixed American | 0.00312% | 32,076 |
| European (non-Finnish) | 9.16e-05% | 1,091,283 |
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.Pro248=
- Coding
- c.744C>T
- MANE Select
- NM_005251
- dbSNP
- rs375784716
- Type
- single nucleotide variant
- Location
- chr16:86568079 (GRCh38)
- Gene constraint
- LOEUF 1.807 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 56.45 · 8 PDB
- Residue 248
- 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-pro248 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown