Is DSC2 p.Thr814= (c.2442G>A) pathogenic?

DSC2 p.Thr814= (c.2442G>A) is classified Likely benign in DSC2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-08-26). Very rare (popmax 0.005%, amr); Associated with arrhythmogenic right ventricular dysplasia 11.

What condition is associated with DSC2 p.Thr814= (c.2442G>A)?

DSC2 p.Thr814= (c.2442G>A) is associated with arrhythmogenic right ventricular dysplasia 11, cardiomyopathy, familial isolated arrhythmogenic right ventricular dysplasia (ClinVar).

How common is DSC2 p.Thr814= (c.2442G>A) in the general population?

DSC2 p.Thr814= (c.2442G>A) is very rare (popmax 0.005%, amr) (gnomAD).

DSC2 p.Thr814=

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.2442G>A · rs750971227 · VCV511117

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

arrhythmogenic right ventricular dysplasia 11

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 -0.63	GERP 0.16
Overall
CADD	6.957	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,010 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00041% 6/1,461,860 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,003
European (non-Finnish)	0.000254%	393,342

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.Thr814=
Coding: c.2442G>A
MANE Select: NM_024422
dbSNP: rs750971227
Type: single nucleotide variant
Location: chr18:31068960 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 77.26 · 3 PDB
Residue 814: 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

arrhythmogenic right ventricular dysplasia 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy familial isolated arrhythmogenic right ventricular dysplasia

For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

Similar variants

DSC2 p.Thr814Ser Uncertain significance ★★ ⚠ same residue
DSC2 p.Thr814Met Conflicting classifications of pathogenicity ★ ⚠ same residue
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-thr814 (accessed [today's date]).

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