Is CTNNB1 p.Ser45Pro (c.133T>C) pathogenic?

CTNNB1 p.Ser45Pro (c.133T>C) is classified Pathogenic/Likely pathogenic in CTNNB1 (ClinVar, No assertion criteria, 4 submitters; last evaluated 1999-07-08). AlphaMissense: likely pathogenic (0.9557); Absent from gnomAD v4.1; Associated with hepatocellular carcinoma.

What condition is associated with CTNNB1 p.Ser45Pro (c.133T>C)?

CTNNB1 p.Ser45Pro (c.133T>C) is associated with hepatocellular carcinoma (ClinVar).

How common is CTNNB1 p.Ser45Pro (c.133T>C) in the general population?

CTNNB1 p.Ser45Pro (c.133T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTNNB1 p.Ser45Pro (c.133T>C)?

AlphaMissense predicts likely pathogenic (score 0.9557) — an in-silico prediction, not a clinical call.

CTNNB1 p.Ser45Pro

c.133T>C · rs121913407 · VCV17589

Pathogenic/Likely pathogenic No assertion criteria

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9557 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hepatocellular carcinoma

Computational evidence

Protein change
AlphaMissense	0.9557	likely pathogenic ✓ concordant with ClinVar
REVEL	0.338	indeterminate
SaProt	LLR -6.97	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.9, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 12 kb · p 2.8e-39 · regional, not allelic
Overall
CADD	29.2	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.

Cancer therapy — CIViC

Disease	Level	Significance
Desmoid Tumor	B	Positive
Desmoid Tumor	B	Better Outcome
Desmoid Tumor	B	Positive

Variant & gene context

Gene: CTNNB1
Protein: p.Ser45Pro
Coding: c.133T>C
MANE Select: NM_001904
dbSNP: rs121913407
Type: single nucleotide variant
Location: chr3:41224645 (GRCh38)
Gene constraint: LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.02 · 50 PDB
Residue 45: the 'disordered' region; a modified residue (phosphoserine); a UniProt-annotated variant site (in hepatocellular carcinoma); a UniProt-annotated variant site (in colorectal cancer); an α-helix

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

Disease context

hepatocellular carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTNNB1 p.Arg474Ter Pathogenic ★★ same condition
CTNNB1 p.Arg515Ter Pathogenic ★★ same condition
CTNNB1 p.Arg95Ter Pathogenic ★★ same condition
CTNNB1 p.Thr41Ala Likely pathogenic ★★ ⚠ same condition
CTNNB1 c.14-4A>G Benign/Likely benign ★★ same condition
CTNNB1 c.1683+17A>G Benign/Likely benign ★★ same condition
CTNNB1 p.Asn287Ser Benign/Likely benign ★★ same condition
CTNNB1 p.Leu774= Benign/Likely benign ★★ 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/ctnnb1-p-ser45pro (accessed [today's date]).

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