TP63 p.Arg337Ter
c.1009C>T · rs113993966 · VCV2429656
Pathogenic/Likely pathogenic
Multiple submitters
Classification
Pathogenic/Likely pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
TP63-related disorder
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 8 of 14 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.6 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 41.0 | 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.Arg337Ter
- Coding
- c.1009C>T
- MANE Select
- NM_003722
- dbSNP
- rs113993966
- Type
- single nucleotide variant
- Location
- chr3:189868596 (GRCh38)
- Gene constraint
- LOEUF 0.296 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.70 · 26 PDB
- Residue 337
- a β-strand; a DNA-binding region; a UniProt-annotated variant site (in adult syndrome; confers novel transcription activation capacity on isoform 6)
Similar variants
- TP63 p.Arg337Gln Pathogenic/Likely pathogenic ★★ same residue
- TP63 p.Arg337Gly Pathogenic ★ same residue
- TP63 p.Arg243Gln Pathogenic/Likely pathogenic ★★ same condition
- TP63 p.Arg243Trp Pathogenic ★★ same condition
- TP63 p.Arg266Gln Pathogenic/Likely pathogenic ★★ same condition
- TP63 p.Arg318Cys Pathogenic ★★ same condition
- TP63 p.Arg319Cys Pathogenic/Likely pathogenic ★★ same condition
- TP63 p.Arg319His 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/tp63-p-arg337ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown