Is CDH2 p.Asp295= (c.885C>T) pathogenic?

CDH2 p.Asp295= (c.885C>T) is classified Benign/Likely benign in CDH2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-02). Rare (popmax 0.997%, afr); Associated with arrhythmogenic right ventricular dysplasia, familial, 14.

What condition is associated with CDH2 p.Asp295= (c.885C>T)?

CDH2 p.Asp295= (c.885C>T) is associated with arrhythmogenic right ventricular dysplasia, familial, 14, agenesis of corpus callosum, cardiac, ocular, and genital syndrome (ClinVar).

How common is CDH2 p.Asp295= (c.885C>T) in the general population?

CDH2 p.Asp295= (c.885C>T) is rare (popmax 0.997%, afr) (gnomAD).

CDH2 p.Asp295=

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.885C>T · rs17493618 · VCV789103

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.997%, afr)

Conditions

arrhythmogenic right ventricular dysplasia, familial, 14

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 -0.88	GERP -5.5
Overall
CADD	3.004	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.997% African / African-American · 748/75,006 alleles

Filtering AF 0.938% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.914%

Overall 0.0557% 899/1,613,740 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.997%	100
Remaining individualsnot grpmax-eligible	0.0816%	1,225
Admixed American	0.0517%	1,935
South Asian	0.00549%	18,214
European (non-Finnish)	0.00534%	18,726
Finnishnot grpmax-eligible	0.00156%	64,022

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: CDH2
Protein: p.Asp295=
Coding: c.885C>T
MANE Select: NM_001792
dbSNP: rs17493618
Type: single nucleotide variant
Location: chr18:28003132 (GRCh38)
Gene constraint: LOEUF 0.336 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.68
Residue 295: a binding site; the cadherin 2 domain

Full CDH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

arrhythmogenic right ventricular dysplasia, familial, 14 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: agenesis of corpus callosum, cardiac, ocular, and genital syndrome

For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

Similar variants

CDH2 c.1344+1G>A Pathogenic/Likely pathogenic ★★ same condition
CDH2 c.702+1G>A Pathogenic/Likely pathogenic ★★ same condition
CDH2 p.Tyr676Cys Pathogenic ★★ same condition
CDH2 c.848-16T>G Uncertain significance ★★ same condition
CDH2 p.Asn378Ser Uncertain significance ★★ ⚠ same condition
CDH2 p.Phe835Leu Uncertain significance ★★ ⚠ same condition
CDH2 p.Thr535Ser Uncertain significance ★★ ⚠ same condition
CDH2 p.Val566Met 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/cdh2-p-asp295 (accessed [today's date]).

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