Is DSG2 p.Lys40Arg (c.119A>G) pathogenic?

DSG2 p.Lys40Arg (c.119A>G) is classified Uncertain significance in DSG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-18). AlphaMissense: likely benign (0.07); Absent from gnomAD v4.1; Associated with arrhythmogenic right ventricular dysplasia 10.

What condition is associated with DSG2 p.Lys40Arg (c.119A>G)?

DSG2 p.Lys40Arg (c.119A>G) is associated with arrhythmogenic right ventricular dysplasia 10 (ClinVar).

How common is DSG2 p.Lys40Arg (c.119A>G) in the general population?

DSG2 p.Lys40Arg (c.119A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSG2 p.Lys40Arg (c.119A>G)?

AlphaMissense predicts likely benign (score 0.07) — an in-silico prediction, not a clinical call.

DSG2 p.Lys40Arg

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.119A>G · VCV3637541

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.07 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

arrhythmogenic right ventricular dysplasia 10

Computational evidence

Protein change
AlphaMissense	0.07	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -6.24	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.29	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 0.78
Regional constraint	o/e 0.93	unconstrained · MANE · 48 kb · p 0.014 · regional, not allelic
Overall
CADD	6.268	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: DSG2
Protein: p.Lys40Arg
Coding: c.119A>G
MANE Select: NM_001943
Type: single nucleotide variant
Location: chr18:31519840 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 65.27 · 12 PDB

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 c.1423+1G>T Likely pathogenic ★★ same condition
DSG2 c.1424-1G>A Likely pathogenic ★★ same condition
DSG2 c.523+1G>T Pathogenic/Likely pathogenic ★★ same condition
DSG2 c.690+1G>A Pathogenic ★★ same condition
DSG2 c.81+1G>T Likely pathogenic ★★ same condition
DSG2 c.829-2A>T Likely pathogenic ★★ same condition
DSG2 p.Arg46Gln Pathogenic/Likely pathogenic ★★ same condition
DSG2 p.Arg46Trp 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-lys40arg (accessed [today's date]).

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