Is DSG2 p.Asp827fs (c.2480_2712del) pathogenic?

DSG2 p.Asp827fs (c.24802712del) is classified Pathogenic in DSG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-09). Absent from gnomAD; Associated with arrhythmogenic right ventricular dysplasia 10.

What condition is associated with DSG2 p.Asp827fs (c.2480_2712del)?

DSG2 p.Asp827fs (c.2480_2712del) is associated with arrhythmogenic right ventricular dysplasia 10 (ClinVar).

How common is DSG2 p.Asp827fs (c.2480_2712del) in the general population?

DSG2 p.Asp827fs (c.2480_2712del) is absent from gnomAD (gnomAD).

DSG2 p.Asp827fs

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.2480_2712del · rs2144359029 · VCV1075858

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

arrhythmogenic right ventricular dysplasia 10

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (15 of 15) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	phastCons 1

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

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: DSG2
Protein: p.Asp827fs
Coding: c.2480_2712del
MANE Select: NM_001943
dbSNP: rs2144359029
Type: Deletion
Location: chr18:31545864 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 65.27 · 12 PDB
Residue 827: a UniProt-annotated variant site (in arvd10; uncertain significance; evidence of residual myocardium, fibrous tissue, fatty tissue, dysmetric and dysmorphic nuclei and prominent cytoplasmic vacuolization; decreases the number of desmosomes at intercalated disks also increases desmosome gap; smaller intercellular gaps, with repeating couplings, abnormally located desmosomes and pale internal plaques); a UniProt-annotated variant site (in arvd10; uncertain significance)

Full DSG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

arrhythmogenic right ventricular dysplasia 10 — 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

DSG2 p.Asp827His Uncertain significance ★★ ⚠ same residue
DSG2 c.2001_2001+5del Likely pathogenic ★★ same condition
DSG2 c.523+1_523+2del Likely pathogenic ★★ same condition
DSG2 p.Asn462fs Pathogenic/Likely pathogenic ★★ same condition
DSG2 p.Leu171fs Pathogenic/Likely pathogenic ★★ same condition
DSG2 p.Phe211fs Pathogenic ★★ same condition
DSG2 p.Thr31fs Pathogenic/Likely pathogenic ★★ same condition
DSG2 p.Val103fs 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/dsg2-p-asp827fs (accessed [today's date]).

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