TP63 p.Ala667fs
c.1999del · VCV3729545
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
TP63-Related Spectrum 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 LoF-intolerant gene |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (14 of 14) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 3.4 | GERP 0.45, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- TP63
- Protein
- p.Ala667fs
- Coding
- c.1999del
- MANE Select
- NM_003722
- Type
- Deletion
- Location
- chr3:189894458 (GRCh38)
- Gene constraint
- LOEUF 0.296 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.70 · 26 PDB
- Residue 667
- a UniProt-annotated variant site (in pof21; results in increased transcriptional activation in luciferase reporter assays; affects oligomerization); a UniProt-annotated variant site (in pof21); a UniProt-annotated variant site (in lms); the 'transactivation inhibition' region
Disease context
TP63-Related Spectrum Disorders
Similar variants
- TP63 c.1213-17del Likely benign ★★ same condition
- TP63 c.192-9_192-8del Benign/Likely benign ★★ same condition
- TP63 p.Arg618fs Pathogenic ★ same condition
- TP63 p.Lys233_Ala234delinsThr Pathogenic ★ same condition
- TP63 p.Ser621fs Pathogenic ★ same condition
- TP63 p.Tyr579fs Pathogenic ★ same condition
- TP63 p.Leu616fs Uncertain significance ★ same condition
- TP63 c.1653-18_1653-5del Likely benign ★ 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/tp63-p-ala667fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown