FOXC2 p.Val298=
c.894G>A · rs367759818 · VCV2816961
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.053%, 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 3.2 | GERP -0.48, phastCons 1 |
| Overall | ||
| CADD | 11.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.053%
East Asian · 16/30,170 alleles
Filtering AF
0.0332%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0271%
Overall
0.00447%
57/1,274,658 alleles · ultra-rare
exomes 36/1,124,122 · genomes 21/150,536 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.053% | 1,886 |
| Remaining individualsnot grpmax-eligible | 0.0447% | 2,237 |
| Admixed American | 0.0352% | 2,840 |
| South Asian | 0.0138% | 7,234 |
| European (non-Finnish) | 0.000591% | 169,283 |
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.Val298=
- Coding
- c.894G>A
- MANE Select
- NM_005251
- dbSNP
- rs367759818
- Type
- single nucleotide variant
- Location
- chr16:86568229 (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.Val298dup Uncertain significance ★★ same residue
- FOXC2 p.Val298fs Likely 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
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-val298 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown