Is DSG2 p.Pro857Ser (c.2569C>T) pathogenic?

DSG2 p.Pro857Ser (c.2569C>T) is classified Conflicting classifications of pathogenicity in DSG2 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0838); Very rare (popmax 0.005%, amr); Associated with arrhythmogenic right ventricular cardiomyopathy.

What condition is associated with DSG2 p.Pro857Ser (c.2569C>T)?

DSG2 p.Pro857Ser (c.2569C>T) is associated with arrhythmogenic right ventricular cardiomyopathy, cardiomyopathy, arrhythmogenic right ventricular dysplasia 10 (ClinVar).

How common is DSG2 p.Pro857Ser (c.2569C>T) in the general population?

DSG2 p.Pro857Ser (c.2569C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about DSG2 p.Pro857Ser (c.2569C>T)?

AlphaMissense predicts likely benign (score 0.0838) — an in-silico prediction, not a clinical call.

DSG2 p.Pro857Ser

c.2569C>T · rs775091459 · VCV571384

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0838 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

arrhythmogenic right ventricular cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.0838	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -5.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.056
Regional constraint	o/e 0.93	unconstrained · MANE · 48 kb · p 0.014 · regional, not allelic
Overall
CADD	10.96	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 0.005% Admixed American · 3/60,010 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000682% 11/1,614,038 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,003
African / African-American	0.004%	24,975
South Asian	0.00329%	30,360
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	8.47e-05%	1,180,034

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.Pro857Ser
Coding: c.2569C>T
dbSNP: rs775091459
Type: single nucleotide variant
Location: chr18:31545955 (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-pro857ser (accessed [today's date]).

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