Is CTNNB1 p.Pro754Ala (c.2260C>G) pathogenic?

CTNNB1 p.Pro754Ala (c.2260C>G) is classified Uncertain significance in CTNNB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-28). AlphaMissense: likely benign (0.1548); Absent from gnomAD v4.1.

How common is CTNNB1 p.Pro754Ala (c.2260C>G) in the general population?

CTNNB1 p.Pro754Ala (c.2260C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTNNB1 p.Pro754Ala (c.2260C>G)?

AlphaMissense predicts likely benign (score 0.1548) — an in-silico prediction, not a clinical call.

CTNNB1 p.Pro754Ala

c.2260C>G · rs2470865652 · VCV2772218

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1548 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1548	likely benign
REVEL	0.255	benign-leaning
SaProt	LLR -6.21	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 2,665 bp · p 0.012 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: CTNNB1
Protein: p.Pro754Ala
Coding: c.2260C>G
MANE Select: NM_001904
dbSNP: rs2470865652
Type: single nucleotide variant
Location: chr3:41239256 (GRCh38)
Gene constraint: LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.02 · 50 PDB
Residue 754: the 'disordered' region; a UniProt-annotated variant site (in nedsdv; the patient also manifest features of exudative vitreoretinopathy)

Full CTNNB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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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/ctnnb1-p-pro754ala (accessed [today's date]).

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