Is DSC2 p.Val458fs (c.1370_1371dup) pathogenic?

DSC2 p.Val458fs (c.13701371dup) is classified Pathogenic in DSC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-04-09). Absent from gnomAD; Associated with arrhythmogenic right ventricular dysplasia 11.

What condition is associated with DSC2 p.Val458fs (c.1370_1371dup)?

DSC2 p.Val458fs (c.1370_1371dup) is associated with arrhythmogenic right ventricular dysplasia 11 (ClinVar).

How common is DSC2 p.Val458fs (c.1370_1371dup) in the general population?

DSC2 p.Val458fs (c.1370_1371dup) is absent from gnomAD (gnomAD).

DSC2 p.Val458fs

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.1370_1371dup · rs1987170019 · VCV852942

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

arrhythmogenic right ventricular dysplasia 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP 0.28, phastCons 0.93

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DSC2
Protein: p.Val458fs
Coding: c.1370_1371dup
MANE Select: NM_024422
dbSNP: rs1987170019
Type: Duplication
Location: chr18:31080244 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 77.26 · 3 PDB
Residue 458: 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

For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

Similar variants

DSC2 p.Val458= Likely benign ★★ same residue
DSC2 p.Leu396fs Pathogenic ★★ same condition
DSC2 c.2126-15dup Likely benign ★★ same condition
DSC2 c.631-13dup Benign/Likely benign ★★ same condition
DSC2 c.70-18dup Benign/Likely benign ★★ same condition
DSC2 c.70-8dup Benign/Likely benign ★★ same condition
DSC2 c.942+13_942+15dup Benign/Likely benign ★★ same condition
DSC2 c.943-9dup Benign/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/dsc2-p-val458fs (accessed [today's date]).

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