FOXC2 p.Glu208=
c.624G>A · rs372749779 · VCV993869
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.09%, sas)
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 2.8 | GERP -1.4, phastCons 1 |
| Overall | ||
| CADD | 8.542 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.09%
South Asian · 898/82,288 alleles
Filtering AF
1.03%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.01%
Overall
0.061%
943/1,545,208 alleles · low-frequency
exomes 887/1,392,980 · genomes 56/152,228 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 1.09% | 92 |
| Remaining individualsnot grpmax-eligible | 0.0587% | 1,705 |
| Middle Eastern | 0.0196% | 5,098 |
| African / African-American | 0.00139% | 72,036 |
| European (non-Finnish) | 0.000689% | 145,065 |
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.Glu208=
- Coding
- c.624G>A
- MANE Select
- NM_005251
- dbSNP
- rs372749779
- Type
- single nucleotide variant
- Location
- chr16:86567959 (GRCh38)
- Gene constraint
- LOEUF 1.807 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 56.45 · 8 PDB
- Residue 208
- the 'disordered' region
Similar variants
- FOXC2 p.Glu208Ala Uncertain significance ★ ⚠ same residue
- 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
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-glu208 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown