Is DSC2 p.Arg375= (c.1125A>G) pathogenic?

DSC2 p.Arg375= (c.1125A>G) is classified Likely benign in DSC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-17). Absent from gnomAD v4.1; Associated with familial isolated arrhythmogenic right ventricular dysplasia.

What condition is associated with DSC2 p.Arg375= (c.1125A>G)?

DSC2 p.Arg375= (c.1125A>G) is associated with familial isolated arrhythmogenic right ventricular dysplasia (ClinVar).

How common is DSC2 p.Arg375= (c.1125A>G) in the general population?

DSC2 p.Arg375= (c.1125A>G) is absent from gnomAD v4.1 (gnomAD).

DSC2 p.Arg375=

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.1125A>G · rs2510948389 · VCV3073420

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

familial isolated arrhythmogenic right ventricular dysplasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -2.3, phastCons 0.99
Overall
CADD	7.491	PHRED · no single calibrated threshold — expert panels disagree

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.Arg375=
Coding: c.1125A>G
MANE Select: NM_024422
dbSNP: rs2510948389
Type: single nucleotide variant
Location: chr18:31082376 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 77.26 · 3 PDB
Residue 375: a β-strand; the cadherin 3 domain

Full DSC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial isolated arrhythmogenic right ventricular dysplasia — 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.Arg375Gln Uncertain significance ★★ ⚠ same residue
DSC2 p.Arg375Gly Uncertain significance ★★ ⚠ same residue
DSC3 p.Arg375Ter Likely pathogenic ★ same residue
DSC2 c.1077+2T>G Uncertain significance ★★ same condition
DSC2 c.1520+6T>C Uncertain significance ★★ same condition
DSC2 c.942+3A>G Uncertain significance ★★ same condition
DSC2 p.Ala138Ser Uncertain significance ★★ ⚠ same condition
DSC2 p.Ala13Val 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/dsc2-p-arg375 (accessed [today's date]).

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