FOXC2 p.Pro412fs
c.1235_1253del · VCV4931688
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
FOXC2-related disorders
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (1 of 1) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 2.8 | GERP -0.81, phastCons 0.99 |
| Region caveats | ||
| Repeat context | tandem | (CGC)n simple repeat · ambiguous alignment · confidence, not pathogenicity |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- FOXC2
- Protein
- p.Pro412fs
- Coding
- c.1235_1253del
- MANE Select
- NM_005251
- Type
- Deletion
- Location
- chr16:86568567 (GRCh38)
- Gene constraint
- LOEUF 1.807 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 56.45 · 8 PDB
- Residue 412
- the 'disordered' region
Disease context
FOXC2-related disorders
Similar variants
- FOXC2 p.Tyr305fs Pathogenic ★★ same condition
- FOXC2 p.Gln63fs Likely pathogenic ★ same condition
- FOXC2 p.Lys68fs Likely pathogenic ★ same condition
- FOXC2 p.Tyr329fs Likely pathogenic same condition
- FOXC2 p.Pro188Leu Uncertain significance ★★ ⚠ same condition
- FOXC2 p.Gln315Ter Pathogenic ★ same condition
- FOXC2 p.Thr385fs Likely pathogenic ★ same condition
- FOXC2 p.Tyr305Ter Likely pathogenic ★ same condition
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-pro412fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown