Is DSC2 p.Glu90= (c.270G>A) pathogenic?

DSC2 p.Glu90= (c.270G>A) is classified Conflicting classifications of pathogenicity in DSC2 (ClinVar, Conflicting submitters, 18 submitters; last evaluated 2026-03-27). Ultra-rare (popmax 0.0944%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DSC2 p.Glu90= (c.270G>A)?

DSC2 p.Glu90= (c.270G>A) is associated with Cardiovascular phenotype, cardiomyopathy, arrhythmogenic right ventricular dysplasia 11 (ClinVar).

How common is DSC2 p.Glu90= (c.270G>A) in the general population?

DSC2 p.Glu90= (c.270G>A) is ultra-rare (popmax 0.0944%, nfe) (gnomAD).

DSC2 p.Glu90=

c.270G>A · rs138643506 · VCV46187

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 18 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0944%, nfe)

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 0.038	GERP -4, phastCons 0.011
Overall
CADD	5.773	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0944% European (non-Finnish) · 1,114/1,179,716 alleles

Filtering AF 0.0898% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0879%

Overall 0.0749% 1,209/1,613,632 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0944%	1,059
Remaining individualsnot grpmax-eligible	0.0816%	1,225
Admixed American	0.045%	2,222
Middle Eastern	0.0331%	3,024
African / African-American	0.016%	6,252
East Asian	0.00223%	44,806
Finnishnot grpmax-eligible	0.00156%	64,012
South Asian	0.0011%	91,042

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.Glu90=
Coding: c.270G>A
MANE Select: NM_024422
dbSNP: rs138643506
Type: single nucleotide variant
Location: chr18:31092185 (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.Glu90Ter Conflicting classifications of pathogenicity ★ 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
DSC2 p.Glu127Ter Pathogenic/Likely 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-glu90 (accessed [today's date]).

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