Is DSC2 p.Phe209fs (c.627del) pathogenic?

DSC2 p.Phe209fs (c.627del) is classified Uncertain significance in DSC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-10). Associated with familial isolated arrhythmogenic right ventricular dysplasia.

What condition is associated with DSC2 p.Phe209fs (c.627del)?

DSC2 p.Phe209fs (c.627del) is associated with familial isolated arrhythmogenic right ventricular dysplasia (ClinVar).

DSC2 p.Phe209fs

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.627del · VCV3386544

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

familial isolated arrhythmogenic right ventricular dysplasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.23	GERP 0.26, phastCons 0.97

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: DSC2
Protein: p.Phe209fs
Coding: c.627del
MANE Select: NM_024422
Type: Deletion
Location: chr18:31089442 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 77.26 · 3 PDB
Residue 209: the cadherin 1 domain

Full DSC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial isolated arrhythmogenic right ventricular dysplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

Similar variants

DSC2 p.Phe209= Likely benign ★★ same residue
DSC2 p.Asp238del Uncertain significance ★★ same condition
DSC2 p.Tyr248_Thr249del Uncertain significance ★★ same condition
DSC2 p.Thr216fs Pathogenic ★ same condition
DSC2 c.943-9del Uncertain significance ★ same condition
DSC2 p.457TV[1] Uncertain significance ★ same condition
DSC2 p.Ala31_Cys32insTer Conflicting classifications of pathogenicity ★ same condition
DSC2 p.Ala718fs Conflicting classifications of pathogenicity ★ 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-phe209fs (accessed [today's date]).

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