Is DSC2 p.Gln116= (c.348A>G) pathogenic?

DSC2 p.Gln116= (c.348A>G) is classified Benign/Likely benign in DSC2 (ClinVar, Multiple submitters, 15 submitters; last evaluated 2026-01-18). Ultra-rare (popmax 0.0989%, sas); Associated with Cardiovascular phenotype.

What condition is associated with DSC2 p.Gln116= (c.348A>G)?

DSC2 p.Gln116= (c.348A>G) is associated with Cardiovascular phenotype, cardiomyopathy, arrhythmogenic right ventricular dysplasia 11 (ClinVar).

How common is DSC2 p.Gln116= (c.348A>G) in the general population?

DSC2 p.Gln116= (c.348A>G) is ultra-rare (popmax 0.0989%, sas) (gnomAD).

DSC2 p.Gln116=

c.348A>G · rs137941742 · VCV163192

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0989%, sas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.79	GERP -0.72, phastCons 0.001
Overall
CADD	4.351	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0989% South Asian · 90/90,960 alleles

Filtering AF 0.0824% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0762%

Overall 0.0356% 574/1,612,054 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0989%	1,011
Middle Eastern	0.0716%	1,396
European (non-Finnish)	0.038%	2,632
Remaining individualsnot grpmax-eligible	0.0305%	3,283
Admixed American	0.0133%	7,496
African / African-American	0.00668%	14,976

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.Gln116=
Coding: c.348A>G
MANE Select: NM_024422
dbSNP: rs137941742
Type: single nucleotide variant
Location: chr18:31092107 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 77.26 · 3 PDB

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

Similar variants

DSC2 p.Gln116Glu Uncertain significance ★★ ⚠ same residue
DSC2 p.Gln116Pro Uncertain significance ★ ⚠ 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
DSC2 p.Gln620Ter 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-gln116 (accessed [today's date]).

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