Is DSG2 p.Ser1111= (c.3333C>T) pathogenic?

DSG2 p.Ser1111= (c.3333C>T) is classified Likely benign in DSG2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-11-06). Very rare (popmax 0.00223%, eas); Associated with arrhythmogenic right ventricular dysplasia 10.

What condition is associated with DSG2 p.Ser1111= (c.3333C>T)?

DSG2 p.Ser1111= (c.3333C>T) is associated with arrhythmogenic right ventricular dysplasia 10, cardiomyopathy (ClinVar).

How common is DSG2 p.Ser1111= (c.3333C>T) in the general population?

DSG2 p.Ser1111= (c.3333C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

DSG2 p.Ser1111=

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.3333C>T · rs143867223 · VCV1730329

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

arrhythmogenic right ventricular dysplasia 10

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.44	GERP -1.3, phastCons 0.49
Overall
CADD	6.65	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,880 alleles

Overall 0.000124% 2/1,614,180 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,880
African / African-American	0.00133%	75,048

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DSG2
Protein: p.Ser1111=
Coding: c.3333C>T
dbSNP: rs143867223
Type: single nucleotide variant
Location: chr18:31546719 (GRCh38)

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

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-ser1111 (accessed [today's date]).

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