Is DSG2 p.Ser4Asn (c.11G>A) pathogenic?

DSG2 p.Ser4Asn (c.11G>A) is classified Uncertain significance in DSG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-09). AlphaMissense: likely benign (0.1848); Absent from gnomAD v4.1; Associated with arrhythmogenic right ventricular dysplasia 10.

What condition is associated with DSG2 p.Ser4Asn (c.11G>A)?

DSG2 p.Ser4Asn (c.11G>A) is associated with arrhythmogenic right ventricular dysplasia 10, cardiomyopathy (ClinVar).

How common is DSG2 p.Ser4Asn (c.11G>A) in the general population?

DSG2 p.Ser4Asn (c.11G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSG2 p.Ser4Asn (c.11G>A)?

AlphaMissense predicts likely benign (score 0.1848) — an in-silico prediction, not a clinical call.

DSG2 p.Ser4Asn

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.11G>A · VCV3718072

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1848 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,262,310)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

arrhythmogenic right ventricular dysplasia 10

Computational evidence

Protein change
AlphaMissense	0.1848	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -7.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 0.76, phastCons 0.98
Regional constraint	o/e 0.93	unconstrained · MANE · 48 kb · p 0.014 · regional, not allelic
Overall
CADD	19.02	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

No allele count reported in gnomAD v4.1 (AN 1,262,310). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DSG2
Protein: p.Ser4Asn
Coding: c.11G>A
MANE Select: NM_001943
Type: single nucleotide variant
Location: chr18:31498262 (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

Also linked: cardiomyopathy

For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

Similar variants

DSG2 p.Ser4Gly Uncertain significance ★★ ⚠ same residue
DSG2 p.Ser4= Likely benign ★★ same residue
DSG2 p.Ser4fs Uncertain significance ★★ same residue
DSG2 p.Ser4Ile Uncertain significance ★ ⚠ same residue
DSG2 p.Ser4Arg Likely benign ★ same residue
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

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-ser4asn (accessed [today's date]).

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