TP63 p.Arg319=
c.957T>C · VCV4965446
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000932%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.5 | GERP -3.9, phastCons 1 |
| Overall | ||
| CADD | 9.223 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000932%
European (non-Finnish) · 11/1,179,950 alleles
Filtering AF
0.0005%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000366%
Overall
0.000682%
11/1,613,916 alleles · very rare
exomes 10/1,461,724 · genomes 1/152,192 · joint denominator
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
- TP63
- Protein
- p.Arg319=
- Coding
- c.957T>C
- MANE Select
- NM_003722
- Type
- single nucleotide variant
- Location
- chr3:189867907 (GRCh38)
- Gene constraint
- LOEUF 0.296 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.70 · 26 PDB
- Residue 319
- a DNA-binding region; a UniProt-annotated variant site (in eec3); a UniProt-annotated variant site (in eec3 and shfm4)
Similar variants
- TP63 p.Arg319Cys Pathogenic/Likely pathogenic ★★ same residue
- TP63 p.Arg319His Pathogenic ★★ same residue
- TP63 p.Arg319Pro Likely pathogenic ★ 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
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-arg319 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown