Is DSC2 p.Arg798Gln (c.2393G>A) pathogenic?

DSC2 p.Arg798Gln (c.2393G>A) is classified Benign in DSC2 (ClinVar, Multiple submitters, 19 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0675); Common (popmax 7.73%, sas) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with DSC2 p.Arg798Gln (c.2393G>A)?

DSC2 p.Arg798Gln (c.2393G>A) is associated with Cardiovascular phenotype, cardiomyopathy, arrhythmogenic right ventricular dysplasia 11 (ClinVar).

What do computational predictors say about DSC2 p.Arg798Gln (c.2393G>A)?

AlphaMissense predicts likely benign (score 0.0675) — an in-silico prediction, not a clinical call.

DSC2 p.Arg798Gln

Q: How common is DSC2 p.Arg798Gln (c.2393G>A) in the general population?

DSC2 p.Arg798Gln (c.2393G>A) is common (popmax 7.73%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2393G>A · rs61731921 · VCV36006

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 19 submitters

AlphaMissense

likely benign

0.0675 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 7.73%, sas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0675	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -9.18	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 -2.2	GERP -3.6
Regional constraint	o/e 0.98	unconstrained · MANE · 34 kb · p 0.48 · regional, not allelic
Overall
CADD	0.36	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 7.73% South Asian · 7,036/91,074 alleles

Filtering AF 7.57% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.51%

Overall 4.58% 73,921/1,613,980 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	11.5%	9
Amishnot grpmax-eligible	10.3%	10
South Asiangrpmax	7.73%	13
European (non-Finnish)	4.6%	22
Remaining individualsnot grpmax-eligible	4.23%	24
Middle Eastern	3.22%	31
Ashkenazi Jewishnot grpmax-eligible	2.84%	35
Admixed American	1.46%	69
African / African-American	0.758%	132
East Asian	0.0602%	1,661

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DSC2
Protein: p.Arg798Gln
Coding: c.2393G>A
MANE Select: NM_024422
dbSNP: rs61731921
Type: single nucleotide variant
Location: chr18:31069009 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 77.26 · 3 PDB
Residue 798: a UniProt-annotated variant site (in arvd11; likely pathogenic; mislocalization of dsc2 to the cytoplasm within intercalated disks of the heart); a UniProt-annotated variant site (in)

Full DSC2 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 11 familial isolated arrhythmogenic right ventricular dysplasia arrhythmogenic right ventricular cardiomyopathy

Similar variants

DSC2 p.Arg798Trp Uncertain significance ★★ ⚠ same residue
DSC2 p.Arg798Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
DSC2 p.Arg798= Likely benign ★ same residue
DSC2 c.1521-1G>A Likely pathogenic ★★ same condition
DSC2 c.1664-1G>A Likely pathogenic ★★ same condition
DSC2 c.354+2T>A Likely pathogenic ★★ same condition
DSC2 c.355-1G>A Likely pathogenic ★★ same condition
DSC2 p.Gln554Ter 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/dsc2-p-arg798gln (accessed [today's date]).

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