Is DSC2 p.Ala699fs (c.2094del) pathogenic?

DSC2 p.Ala699fs (c.2094del) is classified Pathogenic in DSC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-01). Associated with arrhythmogenic right ventricular dysplasia 11.

What condition is associated with DSC2 p.Ala699fs (c.2094del)?

DSC2 p.Ala699fs (c.2094del) is associated with arrhythmogenic right ventricular dysplasia 11 (ClinVar).

DSC2 p.Ala699fs

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.2094del · VCV3655241

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 13 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.9	GERP 2, phastCons 1

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

Variant & gene context

Gene: DSC2
Protein: p.Ala699fs
Coding: c.2094del
MANE Select: NM_024422
Type: Deletion
Location: chr18:31071636 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 77.26 · 3 PDB
Residue 699: 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.Ala699Val Uncertain significance ★★ ⚠ same residue
DSC2 p.Ala699Glu Uncertain significance ★ ⚠ same residue
DSC2 p.Ala699= Likely benign ★ same residue
DSC2 p.Gln158fs Pathogenic/Likely pathogenic ★★ same condition
DSC2 p.Ile26fs Pathogenic/Likely pathogenic ★★ same condition
DSC2 p.Leu229fs Pathogenic ★★ same condition
DSC2 p.Lys42fs Pathogenic/Likely pathogenic ★★ same condition
DSC2 p.Phe708fs Pathogenic/Likely 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-ala699fs (accessed [today's date]).

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