TP63 p.His536=
c.1608C>T · rs768312639 · VCV763473
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0201%, eas)
Conditions
1
TP63-Related Spectrum Disorders
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 4 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 10.94 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0201%
East Asian · 9/44,860 alleles
Filtering AF
0.0104%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00779%
Overall
0.000681%
11/1,614,144 alleles · ultra-rare
exomes 11/1,461,846 · genomes 0/152,298 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0201% | 4,984 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,254 |
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.His536=
- Coding
- c.1608C>T
- MANE Select
- NM_003722
- dbSNP
- rs768312639
- Type
- single nucleotide variant
- Location
- chr3:189889440 (GRCh38)
- Gene constraint
- LOEUF 0.296 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.70 · 26 PDB
Disease context
TP63-Related Spectrum Disorders
Similar variants
- TP63 p.His536Leu Uncertain significance ★ ⚠ same residue
- TP63 p.His536Tyr Uncertain significance ★ same residue
- TP63 p.Arg318His Pathogenic/Likely pathogenic ★★ same condition
- TP63 p.Cys561Tyr Likely pathogenic ★★ same condition
- TP63 p.Gly173Arg Pathogenic/Likely pathogenic ★★ same condition
- TP63 p.Gly173Asp Pathogenic/Likely pathogenic ★★ same condition
- TP63 p.Gly336Asp Pathogenic/Likely pathogenic ★★ same condition
- TP63 p.Gly557Val Pathogenic/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/tp63-p-his536 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown