Is TP63 p.Ala641Val (c.1922C>T) pathogenic?

TP63 p.Ala641Val (c.1922C>T) is classified Likely pathogenic in TP63 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-29). AlphaMissense: likely pathogenic (0.9579); Absent from gnomAD v4.1.

How common is TP63 p.Ala641Val (c.1922C>T) in the general population?

TP63 p.Ala641Val (c.1922C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TP63 p.Ala641Val (c.1922C>T)?

AlphaMissense predicts likely pathogenic (score 0.9579) — an in-silico prediction, not a clinical call.

TP63 p.Ala641Val

c.1922C>T · rs1064793283 · VCV418521

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9579 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9579	likely pathogenic ✓ concordant with ClinVar
REVEL	0.558	indeterminate
SaProt	LLR -6.43	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.8, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 26 kb · p 4.9e-05 · regional, not allelic
Overall
CADD	25.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TP63
Protein: p.Ala641Val
Coding: c.1922C>T
MANE Select: NM_003722
dbSNP: rs1064793283
Type: single nucleotide variant
Location: chr3:189894381 (GRCh38)
Gene constraint: LOEUF 0.296 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 63.70 · 26 PDB
Residue 641: a UniProt-annotated variant site (in pof21; results in increased transcriptional activation in luciferase reporter assays; affects oligomerization); a UniProt-annotated variant site (in pof21); the 'transactivation inhibition' region

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

Similar variants

TP63 p.Ala354Glu Likely pathogenic ★★ same type
TP63 p.Arg243Gln Pathogenic/Likely pathogenic ★★ same type
TP63 p.Arg243Trp Pathogenic ★★ same type
TP63 p.Arg266Gln Pathogenic/Likely pathogenic ★★ same type
TP63 p.Arg318Cys Pathogenic ★★ same type
TP63 p.Arg318His Pathogenic/Likely pathogenic ★★ same type
TP63 p.Arg319Cys Pathogenic/Likely pathogenic ★★ same type
TP63 p.Arg319His Pathogenic ★★ same type

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-ala641val (accessed [today's date]).

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