Is TP63 p.Val267Ile (c.799G>A) pathogenic?

TP63 p.Val267Ile (c.799G>A) is classified Uncertain significance in TP63 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-10-13). AlphaMissense: likely benign (0.3123); Very rare (popmax 0.00127%, nfe); Associated with TP63-Related Spectrum Disorders.

What condition is associated with TP63 p.Val267Ile (c.799G>A)?

TP63 p.Val267Ile (c.799G>A) is associated with TP63-Related Spectrum Disorders, ADULT syndrome (ClinVar).

How common is TP63 p.Val267Ile (c.799G>A) in the general population?

TP63 p.Val267Ile (c.799G>A) is very rare (popmax 0.00127%, nfe) (gnomAD).

What do computational predictors say about TP63 p.Val267Ile (c.799G>A)?

AlphaMissense predicts likely benign (score 0.3123) — an in-silico prediction, not a clinical call.

TP63 p.Val267Ile

c.799G>A · rs768752805 · VCV1054108

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3123 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

TP63-Related Spectrum Disorders

Computational evidence

Protein change
AlphaMissense	0.3123	likely benign
REVEL	0.599	indeterminate
SaProt	LLR -10.16	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 58 kb · p 2.4e-11 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00127% European (non-Finnish) · 15/1,179,990 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.000991% 16/1,613,870 alleles · very rare exomes 15/1,461,792 · genomes 1/152,078 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00127%	78,666
South Asian	0.0011%	91,080

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.Val267Ile
Coding: c.799G>A
MANE Select: NM_003722
dbSNP: rs768752805
Type: single nucleotide variant
Location: chr3:189866714 (GRCh38)
Gene constraint: LOEUF 0.296 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 63.70 · 26 PDB
Residue 267: a β-strand; a DNA-binding region

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

Disease context

TP63-Related Spectrum Disorders

Also linked: ADULT syndrome

Similar variants

TP63 p.Arg243Trp Pathogenic ★★ same condition
TP63 p.Arg266Gln Pathogenic/Likely pathogenic ★★ same condition
TP63 p.Arg318His Pathogenic/Likely pathogenic ★★ same condition
TP63 p.Arg337Gln Pathogenic/Likely pathogenic ★★ same condition
TP63 p.Arg343Gln 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

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-val267ile (accessed [today's date]).

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