TP63 p.Arg393Ter
c.1177C>T · rs941268998 · VCV381462
Pathogenic/Likely pathogenic
Multiple submitters
Classification
Pathogenic/Likely pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 9 of 14 |
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 3.3 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 42.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- TP63
- Protein
- p.Arg393Ter
- Coding
- c.1177C>T
- MANE Select
- NM_003722
- dbSNP
- rs941268998
- Type
- single nucleotide variant
- Location
- chr3:189869371 (GRCh38)
- Gene constraint
- LOEUF 0.296 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.70 · 26 PDB
- Residue 393
- the 'disordered' region
Similar variants
- TP63 p.Arg393= Likely benign ★ same residue
- TP63 p.Ala354Glu Likely pathogenic ★★ same type
- TP63 p.Arg243Gln Pathogenic/Likely pathogenic ★★ same type
- TP63 p.Arg243Trp Pathogenic ★★ same type
- TP63 p.Arg266Gln Pathogenic/Likely pathogenic ★★ same type
- TP63 p.Arg318Cys Pathogenic ★★ same type
- TP63 p.Arg318His Pathogenic/Likely pathogenic ★★ same type
- TP63 p.Arg319Cys Pathogenic/Likely pathogenic ★★ 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/tp63-p-arg393ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown