TP63 p.His236=
c.708C>T · rs1217750983 · VCV1151667
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00891%, 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 -2.3 | GERP -3.9 |
| Overall | ||
| CADD | 7.125 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00891%
East Asian · 4/44,874 alleles
Filtering AF
0.00298%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0018%
Overall
0.000496%
8/1,613,948 alleles · very rare
exomes 6/1,461,838 · genomes 2/152,110 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00891% | 11,218 |
| Finnishnot grpmax-eligible | 0.00156% | 64,024 |
| South Asian | 0.0011% | 91,082 |
| European (non-Finnish) | 0.000169% | 590,005 |
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.His236=
- Coding
- c.708C>T
- MANE Select
- NM_003722
- dbSNP
- rs1217750983
- Type
- single nucleotide variant
- Location
- chr3:189864360 (GRCh38)
- Gene constraint
- LOEUF 0.296 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.70 · 26 PDB
- Residue 236
- an α-helix; a DNA-binding region
Disease context
TP63-Related Spectrum Disorders
Similar variants
- TP63 p.His236Pro Likely pathogenic ★ 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
- TP63 p.His247Arg 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-his236 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown