Is TP63 p.Arg243Trp (c.727C>T) pathogenic?

TP63 p.Arg243Trp (c.727C>T) is classified Pathogenic in TP63 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2024-12-01). AlphaMissense: likely pathogenic (0.9996); No allele count reported in gnomAD v4.1 (AN 1,613,904); Associated with TP63-related disorder.

What condition is associated with TP63 p.Arg243Trp (c.727C>T)?

TP63 p.Arg243Trp (c.727C>T) is associated with TP63-related disorder, ADULT syndrome, ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (ClinVar).

How common is TP63 p.Arg243Trp (c.727C>T) in the general population?

TP63 p.Arg243Trp (c.727C>T) is no allele count reported in gnomAD v4.1 (AN 1,613,904) (gnomAD).

What do computational predictors say about TP63 p.Arg243Trp (c.727C>T)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

TP63 p.Arg243Trp

c.727C>T · rs121908835 · VCV6527

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,904)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

TP63-related disorder

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic ✓ concordant with ClinVar · top 6% in TP63
REVEL	0.953	strongly pathogenic-leaning
SaProt	LLR -16.45	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP 1.9, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 58 kb · p 2.4e-11 · regional, not allelic
Overall
CADD	26.6	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

No allele count reported in gnomAD v4.1 (AN 1,613,904). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TP63
Protein: p.Arg243Trp
Coding: c.727C>T
MANE Select: NM_003722
dbSNP: rs121908835
Type: single nucleotide variant
Location: chr3:189864379 (GRCh38)
Gene constraint: LOEUF 0.296 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 63.70 · 26 PDB
Residue 243: a DNA-binding region; a UniProt-annotated variant site (in eec3)

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

Disease context

Also linked: ADULT syndrome ankyloblepharon-ectodermal defects-cleft lip/palate syndrome Rapp-Hodgkin syndrome limb-mammary syndrome ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3 split hand-foot malformation 4 orofacial cleft 8 premature ovarian failure 21

Similar variants

TP63 p.Arg243Gln Pathogenic/Likely pathogenic ★★ same residue
TP63 p.Ala354Glu Likely pathogenic ★★ same condition
TP63 p.Arg266Gln Pathogenic/Likely pathogenic ★★ same condition
TP63 p.Arg318Cys Pathogenic ★★ same condition
TP63 p.Arg318His Pathogenic/Likely pathogenic ★★ same condition
TP63 p.Arg319Cys Pathogenic/Likely pathogenic ★★ same condition
TP63 p.Arg319His Pathogenic ★★ same condition
TP63 p.Arg337Gln 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-arg243trp (accessed [today's date]).

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