Is CTNNB1 p.Ser29Cys (c.86C>G) pathogenic?

CTNNB1 p.Ser29Cys (c.86C>G) is classified Uncertain significance in CTNNB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-01). AlphaMissense: ambiguous (0.4318); Absent from gnomAD v4.1.

How common is CTNNB1 p.Ser29Cys (c.86C>G) in the general population?

CTNNB1 p.Ser29Cys (c.86C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTNNB1 p.Ser29Cys (c.86C>G)?

AlphaMissense predicts ambiguous (score 0.4318) — an in-silico prediction, not a clinical call.

CTNNB1 p.Ser29Cys

c.86C>G · rs2078130210 · VCV2653694

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4318 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4318	ambiguous
REVEL	0.227	benign-leaning
SaProt	LLR -9.12	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 564 bp · p 3.3e-07 · regional, not allelic
Overall
CADD	26.0	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: CTNNB1
Protein: p.Ser29Cys
Coding: c.86C>G
MANE Select: NM_001904
dbSNP: rs2078130210
Type: single nucleotide variant
Location: chr3:41224598 (GRCh38)
Gene constraint: LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.02 · 50 PDB
Residue 29: a modified residue (phosphoserine; by gsk3-beta); a UniProt-annotated variant site (in hepatocellular carcinoma); a turn

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

Similar variants

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
CTNNB1 p.Arg587Ter Pathogenic/Likely pathogenic ★★ same type
CTNNB1 p.Arg661Ter Pathogenic/Likely 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-ser29cys (accessed [today's date]).

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