Is TP63 p.Cys312Phe (c.935G>T) pathogenic?

TP63 p.Cys312Phe (c.935G>T) is classified Likely pathogenic in TP63 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-29). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1; Associated with TP63-Related Spectrum Disorders.

What condition is associated with TP63 p.Cys312Phe (c.935G>T)?

TP63 p.Cys312Phe (c.935G>T) is associated with TP63-Related Spectrum Disorders (ClinVar).

How common is TP63 p.Cys312Phe (c.935G>T) in the general population?

TP63 p.Cys312Phe (c.935G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TP63 p.Cys312Phe (c.935G>T)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

TP63 p.Cys312Phe

c.935G>T · rs1057520664 · VCV651785

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

TP63-Related Spectrum Disorders

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic ✓ concordant with ClinVar · top 6% in TP63
REVEL	0.952	strongly pathogenic-leaning
SaProt	LLR -16.79	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.35	constrained · MANE · 1,862 bp · p 2.1e-09 · regional, not allelic
Overall
CADD	29.7	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.Cys312Phe
Coding: c.935G>T
MANE Select: NM_003722
dbSNP: rs1057520664
Type: single nucleotide variant
Location: chr3:189867885 (GRCh38)
Gene constraint: LOEUF 0.296 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 63.70 · 26 PDB
Residue 312: a binding site; a DNA-binding 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.Cys312= Likely benign ★ same residue
TP63 p.Cys312Gly Likely pathogenic ★ same residue
TP63 p.Cys312Tyr 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

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-cys312phe (accessed [today's date]).

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