Is CTNNB1 p.Thr574= (c.1722C>T) pathogenic?

CTNNB1 p.Thr574= (c.1722C>T) is classified Likely benign in CTNNB1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-11). Very rare (popmax 0.00988%, sas); Associated with Inborn genetic diseases.

What condition is associated with CTNNB1 p.Thr574= (c.1722C>T)?

CTNNB1 p.Thr574= (c.1722C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CTNNB1 p.Thr574= (c.1722C>T) in the general population?

CTNNB1 p.Thr574= (c.1722C>T) is very rare (popmax 0.00988%, sas) (gnomAD).

CTNNB1 p.Thr574=

c.1722C>T · rs566776791 · VCV1642045

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00988%, sas)

Conditions

Inborn genetic diseases

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 -8.1	GERP -4.2
Overall
CADD	4.275	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00988% South Asian · 9/91,072 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00375%

Overall 0.00161% 26/1,614,010 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00988%	10,119
Remaining individualsnot grpmax-eligible	0.0032%	31,250
African / African-American	0.00267%	37,503
European (non-Finnish)	0.0011%	90,766

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.Thr574=
Coding: c.1722C>T
MANE Select: NM_001904
dbSNP: rs566776791
Type: single nucleotide variant
Location: chr3:41235762 (GRCh38)
Gene constraint: LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.02 · 50 PDB
Residue 574: an α-helix; a UniProt-annotated variant site (in nedsdv; the patient also manifest features of exudative vitreoretinopathy)

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-thr574 (accessed [today's date]).

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