Is DSG2 p.Val158fs (c.472del) pathogenic?

DSG2 p.Val158fs (c.472del) is classified Likely pathogenic in DSG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-21). Associated with arrhythmogenic right ventricular cardiomyopathy.

What condition is associated with DSG2 p.Val158fs (c.472del)?

DSG2 p.Val158fs (c.472del) is associated with arrhythmogenic right ventricular cardiomyopathy (ClinVar).

DSG2 p.Val158fs

c.472del · VCV4851280

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

arrhythmogenic right ventricular cardiomyopathy

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 5 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -7.3

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

Variant & gene context

Gene: DSG2
Protein: p.Val158fs
Coding: c.472del
MANE Select: NM_001943
Type: Deletion
Location: chr18:31521192 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 65.27 · 12 PDB
Residue 158: a UniProt-annotated variant site (in); the cadherin 1 domain; a β-strand

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

Disease context

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

Similar variants

DSG2 p.Val158= Likely benign ★★ same residue
DSG2 p.Val158Gly Benign/Likely benign ★★ ⚠ same residue
DSG2 c.1423+5del Uncertain significance ★★ same condition
DSG2 c.828_828+2del Uncertain significance ★★ same condition
DSG2 p.Glu339_Val340insTer Likely pathogenic ★ same condition
DSG2 p.Gly640fs Pathogenic ★ same condition
DSG2 c.691-7_691-3del Conflicting classifications of pathogenicity ★ same condition
DSG2 c.-5del Uncertain significance ★ 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-val158fs (accessed [today's date]).

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