Is DSC2 p.Glu782Ter (c.2344G>T) pathogenic?

DSC2 p.Glu782Ter (c.2344G>T) is classified Pathogenic in DSC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). Absent from gnomAD v4.1; Associated with arrhythmogenic right ventricular dysplasia 11.

What condition is associated with DSC2 p.Glu782Ter (c.2344G>T)?

DSC2 p.Glu782Ter (c.2344G>T) is associated with arrhythmogenic right ventricular dysplasia 11 (ClinVar).

How common is DSC2 p.Glu782Ter (c.2344G>T) in the general population?

DSC2 p.Glu782Ter (c.2344G>T) is absent from gnomAD v4.1 (gnomAD).

DSC2 p.Glu782Ter

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.2344G>T · VCV4738258

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

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/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 15 of 16
Splicing
SpliceAI	Δ0.35	donor gain · deltas
Pangolin	Δ0.25	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.7	GERP 2, phastCons 0.99
Overall
CADD	43.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Glu782Ter
Coding: c.2344G>T
MANE Select: NM_024422
Type: single nucleotide variant
Location: chr18:31069058 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 77.26 · 3 PDB
Residue 782: a UniProt-annotated variant site (in arvd11; likely pathogenic; mislocalization of dsc2 to the cytoplasm within intercalated disks of the heart)

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

For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

Similar variants

DSC2 p.Glu782Lys Uncertain significance ★★ ⚠ 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
DSC2 p.Gln620Ter Pathogenic ★★ same condition
DSC2 p.Glu127Ter Pathogenic/Likely pathogenic ★★ same condition
DSC2 p.Glu593Ter 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-glu782ter (accessed [today's date]).

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