Is CTNND2 p.Phe563Val (c.1687T>G) pathogenic?

CTNND2 p.Phe563Val (c.1687T>G) is classified Likely pathogenic in CTNND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-07). AlphaMissense: likely pathogenic (0.9948); Absent from gnomAD v4.1; Associated with CTNND2-related disorder.

What condition is associated with CTNND2 p.Phe563Val (c.1687T>G)?

CTNND2 p.Phe563Val (c.1687T>G) is associated with CTNND2-related disorder (ClinVar).

How common is CTNND2 p.Phe563Val (c.1687T>G) in the general population?

CTNND2 p.Phe563Val (c.1687T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTNND2 p.Phe563Val (c.1687T>G)?

AlphaMissense predicts likely pathogenic (score 0.9948) — an in-silico prediction, not a clinical call.

CTNND2 p.Phe563Val

c.1687T>G · rs2546872978 · VCV2630604

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9948 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CTNND2-related disorder

Computational evidence

Protein change
AlphaMissense	0.9948	likely pathogenic ✓ concordant with ClinVar · top 10% in CTNND2
REVEL	0.301	indeterminate
SaProt	LLR -11.34	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.9, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 147 kb · p 2.9e-06 · regional, not allelic
Overall
CADD	27.5	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: CTNND2
Protein: p.Phe563Val
Coding: c.1687T>G
MANE Select: NM_001332
dbSNP: rs2546872978
Type: single nucleotide variant
Location: chr5:11236765 (GRCh38)
Gene constraint: LOEUF 0.228 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 58.88

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

Disease context

CTNND2-related disorder

Similar variants

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
CTNND2 c.3212-9T>C Likely benign 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-phe563val (accessed [today's date]).

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