Is TP63 p.Asp83Val (c.248A>T) pathogenic?

TP63 p.Asp83Val (c.248A>T) is classified Uncertain significance in TP63 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-03). AlphaMissense: likely benign (0.093); Very rare (popmax 0.00801%, afr); Associated with TP63-Related Spectrum Disorders.

What condition is associated with TP63 p.Asp83Val (c.248A>T)?

TP63 p.Asp83Val (c.248A>T) is associated with TP63-Related Spectrum Disorders (ClinVar).

How common is TP63 p.Asp83Val (c.248A>T) in the general population?

TP63 p.Asp83Val (c.248A>T) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about TP63 p.Asp83Val (c.248A>T)?

AlphaMissense predicts likely benign (score 0.093) — an in-silico prediction, not a clinical call.

TP63 p.Asp83Val

c.248A>T · rs761960474 · VCV2904475

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.093 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

TP63-Related Spectrum Disorders

Computational evidence

Protein change
AlphaMissense	0.093	likely benign
REVEL	0.5	indeterminate
SaProt	LLR -8.56	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP 0.92, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 177 kb · p 0.031 · regional, not allelic
Overall
CADD	19.05	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,906 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.000496% 8/1,614,044 alleles · very rare exomes 3/1,461,852 · genomes 5/152,192 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,484
Admixed American	0.00333%	30,005

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.Asp83Val
Coding: c.248A>T
MANE Select: NM_003722
dbSNP: rs761960474
Type: single nucleotide variant
Location: chr3:189738698 (GRCh38)
Gene constraint: LOEUF 0.296 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 63.70 · 26 PDB
Residue 83: the 'transcription activation' region

Full TP63 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

TP63-Related Spectrum Disorders

Similar variants

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
TP63 p.His247Tyr 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-asp83val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown