Is CTNND2 p.Pro515= (c.1545A>G) pathogenic?

CTNND2 p.Pro515= (c.1545A>G) is classified Likely benign in CTNND2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-24). Ultra-rare (popmax 0.0115%, nfe); Associated with CTNND2-related disorder.

What condition is associated with CTNND2 p.Pro515= (c.1545A>G)?

CTNND2 p.Pro515= (c.1545A>G) is associated with CTNND2-related disorder (ClinVar).

How common is CTNND2 p.Pro515= (c.1545A>G) in the general population?

CTNND2 p.Pro515= (c.1545A>G) is ultra-rare (popmax 0.0115%, nfe) (gnomAD).

CTNND2 p.Pro515=

c.1545A>G · rs747089324 · VCV3039174

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0115%, nfe)

Conditions

CTNND2-related disorder

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 -6	GERP -4.5
Overall
CADD	1.813	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0115% European (non-Finnish) · 134/1,166,776 alleles

Filtering AF 0.00988% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00928%

Overall 0.00925% 147/1,589,412 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0115%	8,707
South Asian	0.0091%	10,990
Remaining individualsnot grpmax-eligible	0.00813%	12,296

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: CTNND2
Protein: p.Pro515=
Coding: c.1545A>G
MANE Select: NM_001332
dbSNP: rs747089324
Type: single nucleotide variant
Location: chr5:11346455 (GRCh38)
Gene constraint: LOEUF 0.228 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 58.88
Residue 515: the 'disordered' region

Full CTNND2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CTNND2-related disorder

Similar variants

CTNND2 p.Phe563Val Likely pathogenic ★ same condition
CTNND2 p.Ala179Thr Uncertain significance ★ ⚠ same condition
CTNND2 p.Asp1222Asn Uncertain significance ★ ⚠ same condition
CTNND2 p.Gly717Glu Uncertain significance ★ same condition
CTNND2 p.Val963Ile Uncertain significance ★ ⚠ same condition
CTNND2 c.439+5G>A Uncertain significance same condition
CTNND2 p.Gly473Ser Uncertain significance ⚠ same condition
CTNND2 p.Met785Ile 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/ctnnd2-p-pro515 (accessed [today's date]).

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