Is CTNNB1 p.Pro526Ser (c.1576C>T) pathogenic?

CTNNB1 p.Pro526Ser (c.1576C>T) is classified Uncertain significance in CTNNB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-16). AlphaMissense: likely benign (0.1578); Absent from gnomAD v4.1.

How common is CTNNB1 p.Pro526Ser (c.1576C>T) in the general population?

CTNNB1 p.Pro526Ser (c.1576C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTNNB1 p.Pro526Ser (c.1576C>T)?

AlphaMissense predicts likely benign (score 0.1578) — an in-silico prediction, not a clinical call.

CTNNB1 p.Pro526Ser

c.1576C>T · rs2125641919 · VCV1721516

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1578 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1578	likely benign
REVEL	0.336	indeterminate
SaProt	LLR -8.92	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 12 kb · p 2.8e-39 · regional, not allelic
Overall
CADD	25.1	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.Pro526Ser
Coding: c.1576C>T
MANE Select: NM_001904
dbSNP: rs2125641919
Type: single nucleotide variant
Location: chr3:41234190 (GRCh38)
Gene constraint: LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.02 · 50 PDB
Residue 526: an α-helix

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

Similar variants

CTNNB1 p.Pro526Leu Uncertain significance ★ ⚠ same residue
CTNNB1 p.Pro526fs Pathogenic ★ same residue
CTNNB1 c.1081+1G>T Pathogenic/Likely pathogenic ★★ same type
CTNNB1 c.1082-1G>C Pathogenic ★★ same type
CTNNB1 c.735-1G>C Pathogenic ★★ same type
CTNNB1 p.Arg474Ter Pathogenic ★★ same type
CTNNB1 p.Arg515Ter Pathogenic ★★ same type
CTNNB1 p.Arg535Ter Pathogenic ★★ same type

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-pro526ser (accessed [today's date]).

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