Is CTNNA1 p.Pro47= (c.141C>G) pathogenic?

CTNNA1 p.Pro47= (c.141C>G) is classified Benign/Likely benign in CTNNA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-09). Absent from gnomAD v4.1; Associated with hereditary diffuse gastric adenocarcinoma.

What condition is associated with CTNNA1 p.Pro47= (c.141C>G)?

CTNNA1 p.Pro47= (c.141C>G) is associated with hereditary diffuse gastric adenocarcinoma (ClinVar).

How common is CTNNA1 p.Pro47= (c.141C>G) in the general population?

CTNNA1 p.Pro47= (c.141C>G) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary diffuse gastric cancer inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

CTNNA1 p.Pro47=

c.141C>G · rs2149656171 · VCV1126992

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary diffuse gastric adenocarcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.65	GERP -0.96, phastCons 0.009
Overall
CADD	7.716	PHRED · no single calibrated threshold — expert panels disagree

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: CTNNA1
Protein: p.Pro47=
Coding: c.141C>G
MANE Select: NM_001903
dbSNP: rs2149656171
Type: single nucleotide variant
Location: chr5:138783212 (GRCh38)
Gene constraint: LOEUF 0.491 · pLI 0.97 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.01 · 10 PDB
Residue 47: the 'involved in homodimerization' region

Full CTNNA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary diffuse gastric adenocarcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary diffuse gastric cancer (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

CTNNA1 p.Pro47Leu Uncertain significance ★★ ⚠ same residue
CTNNA1 p.Pro47Ser Uncertain significance ★ ⚠ same residue
CTNNA1 c.105+1G>C Likely pathogenic ★★ same condition
CTNNA1 c.1899+1G>C Likely pathogenic ★★ same condition
CTNNA1 c.468+1G>C Likely pathogenic ★★ same condition
CTNNA1 c.468+1G>T Likely pathogenic ★★ same condition
CTNNA1 p.Arg121Ter Pathogenic/Likely pathogenic ★★ same condition
CTNNA1 p.Arg332Ter Pathogenic ★★ 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/ctnna1-p-pro47 (accessed [today's date]).

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