Is DSC2 p.Glu467= (c.1401G>A) pathogenic?

DSC2 p.Glu467= (c.1401G>A) is classified Conflicting classifications of pathogenicity in DSC2 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-08-01). Very rare (popmax 0.00381%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DSC2 p.Glu467= (c.1401G>A)?

DSC2 p.Glu467= (c.1401G>A) is associated with Cardiovascular phenotype, cardiomyopathy, arrhythmogenic right ventricular dysplasia 11 (ClinVar).

How common is DSC2 p.Glu467= (c.1401G>A) in the general population?

DSC2 p.Glu467= (c.1401G>A) is very rare (popmax 0.00381%, nfe) (gnomAD).

DSC2 p.Glu467=

c.1401G>A · rs977781359 · VCV701403

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00381%, 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 0.089	GERP -1.7, phastCons 0.93
Overall
CADD	6.992	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00381% European (non-Finnish) · 45/1,180,014 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.00285% 46/1,613,930 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00381%	26,223
African / African-American	0.00134%	74,894

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.Glu467=
Coding: c.1401G>A
MANE Select: NM_024422
dbSNP: rs977781359
Type: single nucleotide variant
Location: chr18:31080215 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 77.26 · 3 PDB
Residue 467: the cadherin 3 domain

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.Glu467Gln Uncertain significance ★★ ⚠ same residue
DSC2 p.Glu467Lys 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-glu467 (accessed [today's date]).

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