Is DSG2 p.Ser960Arg (c.2880C>G) pathogenic?

DSG2 p.Ser960Arg (c.2880C>G) is classified Conflicting classifications of pathogenicity in DSG2 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-01-29). AlphaMissense: likely benign (0.2736); Ultra-rare (popmax 0.0161%, afr); Associated with Cardiovascular phenotype.

What condition is associated with DSG2 p.Ser960Arg (c.2880C>G)?

DSG2 p.Ser960Arg (c.2880C>G) is associated with Cardiovascular phenotype, cardiomyopathy, arrhythmogenic right ventricular dysplasia 10 (ClinVar).

How common is DSG2 p.Ser960Arg (c.2880C>G) in the general population?

DSG2 p.Ser960Arg (c.2880C>G) is ultra-rare (popmax 0.0161%, afr) (gnomAD).

What do computational predictors say about DSG2 p.Ser960Arg (c.2880C>G)?

AlphaMissense predicts likely benign (score 0.2736) — an in-silico prediction, not a clinical call.

DSG2 p.Ser960Arg

c.2880C>G · rs374807974 · VCV199793

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.2736 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0161%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.2736	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -7.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.096	phastCons 0.89
Regional constraint	o/e 0.93	unconstrained · MANE · 48 kb · p 0.014 · regional, not allelic
Overall
CADD	19.28	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0161% African / African-American · 12/74,592 alleles

Filtering AF 0.00925% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00725%

Overall 0.00118% 19/1,603,384 alleles · ultra-rare exomes 9/1,451,258 · genomes 10/152,126 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0161%	6,216
East Asian	0.00893%	11,197
Admixed American	0.00169%	59,330
Remaining individualsnot grpmax-eligible	0.00161%	61,950
European (non-Finnish)	8.52e-05%	1,174,256

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.Ser960Arg
Coding: c.2880C>G
MANE Select: NM_001943
dbSNP: rs374807974
Type: single nucleotide variant
Location: chr18:31546266 (GRCh38)

Full DSG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy arrhythmogenic right ventricular dysplasia 10 arrhythmogenic right ventricular cardiomyopathy

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-ser960arg (accessed [today's date]).

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