TP63 p.Ala354=
c.1062G>A · rs34841666 · VCV1613887
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.388%, 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 -6.7 | GERP -3.9 |
| Overall | ||
| CADD | 6.669 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.388%
South Asian · 353/91,082 alleles
Filtering AF
0.354%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.341%
Overall
0.0269%
435/1,614,106 alleles · rare
exomes 415/1,461,832 · genomes 20/152,274 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.388% | 258 |
| Remaining individualsnot grpmax-eligible | 0.0352% | 2,841 |
| Middle Eastern | 0.0165% | 6,062 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0101% | 9,868 |
| Admixed American | 0.00667% | 15,002 |
| European (non-Finnish) | 0.00424% | 23,600 |
| African / African-American | 0.00267% | 37,519 |
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.Ala354=
- Coding
- c.1062G>A
- MANE Select
- NM_003722
- dbSNP
- rs34841666
- Type
- single nucleotide variant
- Location
- chr3:189868649 (GRCh38)
- Gene constraint
- LOEUF 0.296 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.70 · 26 PDB
- Residue 354
- an α-helix; a DNA-binding region; the 'disordered' region; the 'interaction with hipk2' region
Disease context
TP63-Related Spectrum Disorders
Similar variants
- TP63 p.Ala354Glu 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-ala354 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown