Is DSG2 p.Ser913fs (c.2736del) pathogenic?

DSG2 p.Ser913fs (c.2736del) is classified Pathogenic in DSG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-16). Associated with arrhythmogenic right ventricular dysplasia 10.

What condition is associated with DSG2 p.Ser913fs (c.2736del)?

DSG2 p.Ser913fs (c.2736del) is associated with arrhythmogenic right ventricular dysplasia 10 (ClinVar).

DSG2 p.Ser913fs

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.2736del · VCV4722919

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 10

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (15 of 15) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.1	phastCons 0.96

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

Variant & gene context

Gene: DSG2
Protein: p.Ser913fs
Coding: c.2736del
MANE Select: NM_001943
Type: Deletion
Location: chr18:31546122 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 65.27 · 12 PDB
Residue 913: a UniProt-annotated variant site (in arvd10; uncertain significance; evidence of residual myocardium, fibrous tissue, fatty tissue, dysmetric and dysmorphic nuclei and prominent cytoplasmic vacuolization; decreases the number of desmosomes at intercalated disks also increases desmosome gap; smaller intercellular gaps, with repeating couplings, abnormally located desmosomes and pale internal plaques); a UniProt-annotated variant site (in arvd10; uncertain significance)

Full DSG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

arrhythmogenic right ventricular dysplasia 10 — 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

DSG2 p.Ser913= Likely benign ★★ same residue
DSG2 p.Ser913Pro Uncertain significance ★ ⚠ same residue
DSG2 c.2001_2001+5del Likely pathogenic ★★ same condition
DSG2 c.523+1_523+2del Likely pathogenic ★★ same condition
DSG2 p.Asn462fs Pathogenic/Likely pathogenic ★★ same condition
DSG2 p.Leu171fs Pathogenic/Likely pathogenic ★★ same condition
DSG2 p.Phe211fs Pathogenic ★★ same condition
DSG2 p.Thr31fs 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/dsg2-p-ser913fs (accessed [today's date]).

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