Is DSC2 p.Glu463del (c.1386AGA[1]) pathogenic?

DSC2 p.Glu463del (c.1386AGA[1]) is classified Uncertain significance in DSC2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-01). Very rare (popmax 0.005%, amr); Associated with cardiomyopathy.

What condition is associated with DSC2 p.Glu463del (c.1386AGA[1])?

DSC2 p.Glu463del (c.1386AGA[1]) is associated with cardiomyopathy, arrhythmogenic right ventricular dysplasia 11 (ClinVar).

How common is DSC2 p.Glu463del (c.1386AGA[1]) in the general population?

DSC2 p.Glu463del (c.1386AGA[1]) is very rare (popmax 0.005%, amr) (gnomAD).

DSC2 p.Glu463del

c.1386AGA[1] · VCV3708207

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

cardiomyopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.97	GERP -4, phastCons 0.99

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,014 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000274% 4/1,461,832 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,005
Remaining individualsnot grpmax-eligible	0.0016%	62,502

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: DSC2
Protein: p.Glu463del
Coding: c.1386AGA[1]
MANE Select: NM_024422
Type: Microsatellite
Location: chr18:31080225 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 77.26 · 3 PDB
Residue 463: a β-strand; the cadherin 3 domain

Full DSC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: arrhythmogenic right ventricular dysplasia 11

Similar variants

DSC2 p.Asn546del Uncertain significance ★★ same condition
DSC2 p.Gly863fs Uncertain significance ★★ same condition
DSC2 p.Gly790del Benign/Likely benign ★★ same condition
DSC2 p.Ser614fs Pathogenic ★ same condition
DSC2 p.Arg653_Asp654insTer Uncertain significance ★ same condition
DSC2 p.Glu878del Uncertain significance ★ same condition
DSC2 p.Gly790_His791insGly Uncertain significance ★ same condition
DSC2 p.Ile231del 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/dsc2-p-glu463del (accessed [today's date]).

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