Is DSG2 p.Ser862= (c.2586T>C) pathogenic?

DSG2 p.Ser862= (c.2586T>C) is classified Benign/Likely benign in DSG2 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-03). Rare (popmax 0.887%, afr); Associated with arrhythmogenic right ventricular cardiomyopathy.

What condition is associated with DSG2 p.Ser862= (c.2586T>C)?

DSG2 p.Ser862= (c.2586T>C) is associated with arrhythmogenic right ventricular cardiomyopathy, cardiomyopathy, arrhythmogenic right ventricular dysplasia 10 (ClinVar).

How common is DSG2 p.Ser862= (c.2586T>C) in the general population?

DSG2 p.Ser862= (c.2586T>C) is rare (popmax 0.887%, afr) (gnomAD).

DSG2 p.Ser862=

c.2586T>C · rs78310842 · VCV44303

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Rare

rare (popmax 0.887%, afr)

Conditions

arrhythmogenic right ventricular cardiomyopathy

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 -6.9
Overall
CADD	0.245	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.887% African / African-American · 666/75,058 alleles

Filtering AF 0.831% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.809%

Overall 0.0477% 770/1,614,180 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.887%	113
Admixed American	0.0966%	1,035
Middle Eastern	0.066%	1,516
Remaining individualsnot grpmax-eligible	0.048%	2,084
East Asian	0.00223%	44,886
South Asian	0.0011%	91,084
European (non-Finnish)	0.000847%	118,002

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.Ser862=
Coding: c.2586T>C
dbSNP: rs78310842
Type: single nucleotide variant
Location: chr18:31545972 (GRCh38)

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

Also linked: cardiomyopathy arrhythmogenic right ventricular dysplasia 10

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-ser862 (accessed [today's date]).

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