FOXC2 p.Glu216=
c.648G>A · rs79883807 · VCV707237
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.82%, afr)
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 4.7 | GERP 0.68, phastCons 1 |
| Overall | ||
| CADD | 11.73 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.82%
African / African-American · 2,019/71,552 alleles
Filtering AF
2.72%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.68%
Overall
0.151%
2,293/1,519,184 alleles · low-frequency
exomes 1,017/1,366,982 · genomes 1,276/152,202 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.82% | 35 |
| Admixed American | 0.277% | 360 |
| Remaining individualsnot grpmax-eligible | 0.213% | 469 |
| Middle Eastern | 0.0811% | 1,233 |
| South Asian | 0.00253% | 39,487 |
| European (non-Finnish) | 0.00227% | 44,142 |
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.Glu216=
- Coding
- c.648G>A
- MANE Select
- NM_005251
- dbSNP
- rs79883807
- Type
- single nucleotide variant
- Location
- chr16:86567983 (GRCh38)
- Gene constraint
- LOEUF 1.807 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 56.45 · 8 PDB
Similar variants
- FOXC2 p.Glu216Ter Pathogenic ★ 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-glu216 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown