Is CTNNB1 p.Ser111Pro (c.331T>C) pathogenic?

CTNNB1 p.Ser111Pro (c.331T>C) is classified Uncertain significance in CTNNB1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-13). AlphaMissense: likely benign (0.215); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CTNNB1 p.Ser111Pro (c.331T>C)?

CTNNB1 p.Ser111Pro (c.331T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CTNNB1 p.Ser111Pro (c.331T>C) in the general population?

CTNNB1 p.Ser111Pro (c.331T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTNNB1 p.Ser111Pro (c.331T>C)?

AlphaMissense predicts likely benign (score 0.215) — an in-silico prediction, not a clinical call.

CTNNB1 p.Ser111Pro

c.331T>C · rs2125620159 · VCV1497122

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.215 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.215	likely benign
REVEL	0.362	indeterminate
SaProt	LLR -6.41	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 0.95, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 12 kb · p 2.8e-39 · regional, not allelic
Overall
CADD	23.0	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.Ser111Pro
Coding: c.331T>C
MANE Select: NM_001904
dbSNP: rs2125620159
Type: single nucleotide variant
Location: chr3:41225043 (GRCh38)
Gene constraint: LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.02 · 50 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTNNB1 p.Arg587Ter Pathogenic/Likely pathogenic ★★ same condition
CTNNB1 p.Leu382Pro Likely pathogenic ★★ same condition
CTNNB1 c.2077-2A>G Uncertain significance ★★ same condition
CTNNB1 p.Ala215Ser Uncertain significance ★★ ⚠ same condition
CTNNB1 p.Ala509Gly Uncertain significance ★★ ⚠ same condition
CTNNB1 p.Ala525Val Uncertain significance ★★ ⚠ same condition
CTNNB1 p.Ala689Thr Uncertain significance ★★ same condition
CTNNB1 p.Arg376Cys 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/ctnnb1-p-ser111pro (accessed [today's date]).

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