Is TP63 p.Pro52= (c.156A>G) pathogenic?

TP63 p.Pro52= (c.156A>G) is classified Likely benign in TP63 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-09). Very rare (popmax 0.00186%, nfe); Associated with ADULT syndrome.

What condition is associated with TP63 p.Pro52= (c.156A>G)?

TP63 p.Pro52= (c.156A>G) is associated with ADULT syndrome, ankyloblepharon-ectodermal defects-cleft lip/palate syndrome, Rapp-Hodgkin syndrome (ClinVar).

How common is TP63 p.Pro52= (c.156A>G) in the general population?

TP63 p.Pro52= (c.156A>G) is very rare (popmax 0.00186%, nfe) (gnomAD).

TP63 p.Pro52=

c.156A>G · rs780898702 · VCV1597542

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

Conditions

ADULT syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.35	GERP -2.1, phastCons 0.001
Overall
CADD	4.945	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00186% European (non-Finnish) · 22/1,179,898 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00149% 24/1,613,894 alleles · very rare exomes 23/1,461,668 · genomes 1/152,226 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00186%	53,632
Remaining individualsnot grpmax-eligible	0.0016%	62,482
African / African-American	0.00133%	74,938

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.Pro52=
Coding: c.156A>G
MANE Select: NM_003722
dbSNP: rs780898702
Type: single nucleotide variant
Location: chr3:189737833 (GRCh38)
Gene constraint: LOEUF 0.296 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 63.70 · 26 PDB
Residue 52: the 'transcription activation' region

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

Disease context

ADULT syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: 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

Similar variants

TP63 p.Ala354Glu Likely pathogenic ★★ same condition
TP63 p.Arg243Gln Pathogenic/Likely pathogenic ★★ same condition
TP63 p.Arg243Trp 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

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-pro52 (accessed [today's date]).

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