Is TP63 p.Arg97Pro (c.290G>C) pathogenic?

TP63 p.Arg97Pro (c.290G>C) is classified Pathogenic in TP63 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2023-04-05). AlphaMissense: likely pathogenic (0.7658); Absent from gnomAD v4.1; Associated with premature ovarian failure 21.

What condition is associated with TP63 p.Arg97Pro (c.290G>C)?

TP63 p.Arg97Pro (c.290G>C) is associated with premature ovarian failure 21, premature menopause (ClinVar).

How common is TP63 p.Arg97Pro (c.290G>C) in the general population?

TP63 p.Arg97Pro (c.290G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TP63 p.Arg97Pro (c.290G>C)?

AlphaMissense predicts likely pathogenic (score 0.7658) — an in-silico prediction, not a clinical call.

TP63 p.Arg97Pro

c.290G>C · rs752080701 · VCV1677243

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7658 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

premature ovarian failure 21

Computational evidence

Protein change
AlphaMissense	0.7658	likely pathogenic ✓ concordant with ClinVar
REVEL	0.714	pathogenic-leaning
SaProt	LLR -3.67	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.3, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 177 kb · p 0.031 · regional, not allelic
Overall
CADD	24.4	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.Arg97Pro
Coding: c.290G>C
MANE Select: NM_003722
dbSNP: rs752080701
Type: single nucleotide variant
Location: chr3:189738740 (GRCh38)
Gene constraint: LOEUF 0.296 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 63.70 · 26 PDB
Residue 97: a UniProt-annotated variant site (in pof21; uncertain significance; results in increased transcriptional activation in a luciferase reporter assay; affects oligomerization); the 'transcription activation' region

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

Disease context

premature ovarian failure 21 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: premature menopause

Similar variants

TP63 p.Arg97Cys Uncertain significance ★★ ⚠ same residue
TP63 p.Arg97His Uncertain significance ★★ ⚠ same residue
TP63 p.Arg243Trp Pathogenic ★★ same condition
TP63 p.Arg343Gln Pathogenic/Likely pathogenic ★★ same condition
TP63 p.Arg7Trp Uncertain significance ★★ ⚠ same condition
TP63 p.Asn381Ser Uncertain significance ★★ ⚠ same condition
TP63 p.Asp121Gly Uncertain significance ★★ ⚠ same condition
TP63 p.Glu680Asp Uncertain significance ★★ ⚠ 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-arg97pro (accessed [today's date]).

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