Is CTNNB1 p.Gln440= (c.1320A>G) pathogenic?

CTNNB1 p.Gln440= (c.1320A>G) is classified Conflicting classifications of pathogenicity in CTNNB1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-02-16). Very rare (popmax 0.0011%, sas).

How common is CTNNB1 p.Gln440= (c.1320A>G) in the general population?

CTNNB1 p.Gln440= (c.1320A>G) is very rare (popmax 0.0011%, sas) (gnomAD).

CTNNB1 p.Gln440=

c.1320A>G · rs2078362860 · VCV1215642

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.42	donor gain · deltas
Constraint at this position
Conservation	phyloP 0.83	GERP -3.9, phastCons 0.97
Overall
CADD	15.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,072 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000889% 13/1,461,890 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,508
South Asiangrpmax	0.0011%	91,072
European (non-Finnish)	0.000932%	107,275

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CTNNB1
Protein: p.Gln440=
Coding: c.1320A>G
MANE Select: NM_001904
dbSNP: rs2078362860
Type: single nucleotide variant
Location: chr3:41233663 (GRCh38)
Gene constraint: LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.02 · 50 PDB
Residue 440: an α-helix

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

Similar variants

CTNNB1 p.Gln440Ter Likely 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
CTNNB1 p.Arg587Ter 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-gln440 (accessed [today's date]).

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