TP63 p.Ala145=
c.435G>C · rs546908184 · VCV197218
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00769%, sas)
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 | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.9 | GERP -5.3 |
| Overall | ||
| CADD | 3.84 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00769%
South Asian · 7/91,074 alleles
Filtering AF
0.00359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00255%
Overall
0.000558%
9/1,614,090 alleles · very rare
exomes 9/1,461,894 · genomes 0/152,196 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00769% | 13,011 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,506 |
| African / African-American | 0.00133% | 74,996 |
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.Ala145=
- Coding
- c.435G>C
- MANE Select
- NM_003722
- dbSNP
- rs546908184
- Type
- single nucleotide variant
- Location
- chr3:189808382 (GRCh38)
- Gene constraint
- LOEUF 0.296 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.70 · 26 PDB
- Residue 145
- the 'disordered' region
Disease context
TP63-Related Spectrum Disorders
Similar variants
- TP63 p.Ala145Glu 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
- 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-ala145 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown