Is DSC2 p.Asn439= (c.1317T>C) pathogenic?

DSC2 p.Asn439= (c.1317T>C) is classified Likely benign in DSC2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-29). Absent from gnomAD v4.1; Associated with arrhythmogenic right ventricular dysplasia 11.

What condition is associated with DSC2 p.Asn439= (c.1317T>C)?

DSC2 p.Asn439= (c.1317T>C) is associated with arrhythmogenic right ventricular dysplasia 11, familial isolated arrhythmogenic right ventricular dysplasia (ClinVar).

How common is DSC2 p.Asn439= (c.1317T>C) in the general population?

DSC2 p.Asn439= (c.1317T>C) is absent from gnomAD v4.1 (gnomAD).

DSC2 p.Asn439=

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.1317T>C · rs1987173870 · VCV1136573

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

arrhythmogenic right ventricular dysplasia 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.76	GERP -4, phastCons 0.96
Overall
CADD	0.937	PHRED · no single calibrated threshold — expert panels disagree

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: DSC2
Protein: p.Asn439=
Coding: c.1317T>C
MANE Select: NM_024422
dbSNP: rs1987173870
Type: single nucleotide variant
Location: chr18:31080299 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 77.26 · 3 PDB
Residue 439: a β-strand; the cadherin 3 domain

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

Disease context

arrhythmogenic right ventricular dysplasia 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial isolated arrhythmogenic right ventricular dysplasia

For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

Similar variants

DSC2 p.Asn439Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
DSC2 p.Asn439Ser Uncertain significance ★ ⚠ same residue
DSC2 p.Asn439Thr Uncertain significance ★ ⚠ same residue
DSC2 p.Asn439fs Pathogenic ★ same residue
DSC2 c.1664-1G>A Likely pathogenic ★★ same condition
DSC2 c.354+2T>A Likely pathogenic ★★ same condition
DSC2 c.355-1G>A Likely pathogenic ★★ same condition
DSC2 p.Gln554Ter Pathogenic ★★ 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-asn439 (accessed [today's date]).

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