Is DSC2 p.Cys671Ser (c.2012_2013delinsCT) pathogenic?

DSC2 p.Cys671Ser (c.20122013delinsCT) is classified Uncertain significance in DSC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-04). Absent from gnomAD; Associated with Cardiovascular phenotype.

What condition is associated with DSC2 p.Cys671Ser (c.2012_2013delinsCT)?

DSC2 p.Cys671Ser (c.2012_2013delinsCT) is associated with Cardiovascular phenotype, arrhythmogenic right ventricular dysplasia 11 (ClinVar).

How common is DSC2 p.Cys671Ser (c.2012_2013delinsCT) in the general population?

DSC2 p.Cys671Ser (c.2012_2013delinsCT) is absent from gnomAD (gnomAD).

DSC2 p.Cys671Ser

c.2012_2013delinsCT · rs869025387 · VCV222559

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.8	GERP -3.8, phastCons 0.024
Regional constraint	o/e 0.98	unconstrained · MANE · 34 kb · p 0.48 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DSC2
Protein: p.Cys671Ser
Coding: c.2012_2013delinsCT
MANE Select: NM_024422
dbSNP: rs869025387
Type: Indel
Location: chr18:31071717 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 77.26 · 3 PDB
Residue 671: the cadherin 5 domain; a UniProt-annotated variant site (in arvd11; likely pathogenic; mislocalization of dsc2 to the cytoplasm within intercalated disks of the heart)

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: arrhythmogenic right ventricular dysplasia 11

Similar variants

DSC2 p.Cys671Tyr Uncertain significance ★★ ⚠ same residue
DSC2 p.Cys671= Likely benign ★★ same residue
DSC2 p.Ala850fs Uncertain significance ★★ same condition
DSC2 p.Thr249Asn Uncertain significance ★★ same condition
DSC2 p.Gln310fs Pathogenic ★ same condition
DSC2 p.Pro153fs Pathogenic ★ same condition
DSC2 p.Ala213Phe Uncertain significance ★ same condition
DSC2 p.Gln287_Val288delinsHisLeu Uncertain significance ★ 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-cys671ser (accessed [today's date]).

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