Is TP63 p.Gln122= (c.366G>A) pathogenic?

TP63 p.Gln122= (c.366G>A) is classified Benign/Likely benign in TP63 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-18). Ultra-rare (popmax 0.0933%, amr); Associated with ADULT syndrome.

What condition is associated with TP63 p.Gln122= (c.366G>A)?

TP63 p.Gln122= (c.366G>A) is associated with ADULT syndrome, ankyloblepharon-ectodermal defects-cleft lip/palate syndrome, Rapp-Hodgkin syndrome (ClinVar).

How common is TP63 p.Gln122= (c.366G>A) in the general population?

TP63 p.Gln122= (c.366G>A) is ultra-rare (popmax 0.0933%, amr) (gnomAD).

TP63 p.Gln122=

c.366G>A · rs201774402 · VCV779747

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0933%, amr)

Conditions

ADULT syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.6, phastCons 1
Overall
CADD	10.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0933% Admixed American · 56/60,030 alleles

Filtering AF 0.0737% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0667%

Overall 0.00353% 57/1,614,212 alleles · ultra-rare exomes 52/1,461,894 · genomes 5/152,318 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0933%	1,072
European (non-Finnish)	8.47e-05%	1,180,043

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.Gln122=
Coding: c.366G>A
MANE Select: NM_003722
dbSNP: rs201774402
Type: single nucleotide variant
Location: chr3:189808313 (GRCh38)
Gene constraint: LOEUF 0.296 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 63.70 · 26 PDB

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.Gln122His Uncertain significance ★ ⚠ same residue
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

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-gln122 (accessed [today's date]).

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