Is DSC2 p.Asn573= (c.1719C>T) pathogenic?

DSC2 p.Asn573= (c.1719C>T) is classified Benign/Likely benign in DSC2 (ClinVar, Multiple submitters, 18 submitters; last evaluated 2026-02-03). Low-frequency (popmax 1.78%, afr); Associated with familial isolated arrhythmogenic right ventricular dysplasia.

What condition is associated with DSC2 p.Asn573= (c.1719C>T)?

DSC2 p.Asn573= (c.1719C>T) is associated with familial isolated arrhythmogenic right ventricular dysplasia, cardiomyopathy, arrhythmogenic right ventricular dysplasia 11 (ClinVar).

How common is DSC2 p.Asn573= (c.1719C>T) in the general population?

DSC2 p.Asn573= (c.1719C>T) is low-frequency (popmax 1.78%, afr) (gnomAD).

DSC2 p.Asn573=

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.1719C>T · rs140167653 · VCV137158

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 18 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.78%, afr)

Conditions

familial isolated arrhythmogenic right ventricular dysplasia

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 -3.2	GERP -4
Overall
CADD	0.145	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.78% African / African-American · 1,336/74,990 alleles

Filtering AF 1.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.67%

Overall 0.098% 1,581/1,613,912 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.78%	56
Admixed American	0.188%	531
Remaining individualsnot grpmax-eligible	0.154%	651
Middle Eastern	0.116%	866
South Asian	0.00769%	13,011
European (non-Finnish)	0.00186%	53,635

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.Asn573=
Coding: c.1719C>T
MANE Select: NM_024422
dbSNP: rs140167653
Type: single nucleotide variant
Location: chr18:31074852 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 77.26 · 3 PDB
Residue 573: a UniProt-annotated variant site (in arvd11; likely pathogenic; mislocalization of dsc2 to the cytoplasm within intercalated disks of the heart); the cadherin 4 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

Also linked: cardiomyopathy arrhythmogenic right ventricular dysplasia 11

For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

Similar variants

DSC2 p.Asn573Asp Uncertain significance ★★ ⚠ same residue
DSC2 p.Asn573_Ser574insTer Pathogenic ★ 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-asn573 (accessed [today's date]).

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