Is DSC2 p.Asn11Ser (c.32A>G) pathogenic?

DSC2 p.Asn11Ser (c.32A>G) is classified Benign in DSC2 (ClinVar, Multiple submitters, 18 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.06); Common (popmax 26.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with DSC2 p.Asn11Ser (c.32A>G)?

DSC2 p.Asn11Ser (c.32A>G) is associated with Cardiovascular phenotype, cardiomyopathy, arrhythmogenic right ventricular dysplasia 11 (ClinVar).

What do computational predictors say about DSC2 p.Asn11Ser (c.32A>G)?

AlphaMissense predicts likely benign (score 0.06) — an in-silico prediction, not a clinical call.

DSC2 p.Asn11Ser

Q: How common is DSC2 p.Asn11Ser (c.32A>G) in the general population?

DSC2 p.Asn11Ser (c.32A>G) is common (popmax 26.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.32A>G · rs868333 · VCV46191

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 18 submitters

AlphaMissense

likely benign

0.06 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 26.9%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.06	likely benign
REVEL	0.146	moderately benign-leaning
SaProt	LLR -4.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.2	GERP -1.1
Regional constraint	o/e 0.98	unconstrained · MANE · 34 kb · p 0.48 · regional, not allelic
Overall
CADD	6.243	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 26.9% African / African-American · 19,270/71,732 alleles

Filtering AF 26.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 26.4%

Overall 1.48% 22,645/1,529,004 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	26.9%	4
Remaining individualsnot grpmax-eligible	1.99%	50
Middle Eastern	1.78%	56
Admixed American	1.67%	60
Ashkenazi Jewishnot grpmax-eligible	1.48%	68
South Asian	0.116%	864
European (non-Finnish)	0.0623%	1,606
East Asian	0.0275%	3,637
Finnishnot grpmax-eligible	0.0218%	4,593

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.Asn11Ser
Coding: c.32A>G
MANE Select: NM_024422
dbSNP: rs868333
Type: single nucleotide variant
Location: chr18:31101940 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 77.26 · 3 PDB
Residue 11: a UniProt-annotated variant site (in)

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: cardiomyopathy arrhythmogenic right ventricular dysplasia 11 familial isolated arrhythmogenic right ventricular dysplasia

Similar variants

DSC2 p.Asn11= Likely benign ★ same residue
DSC2 p.Asn11_Gly12delinsSerArg Benign/Likely benign ★★ same residue
DSC2 c.1521-1G>A Likely pathogenic ★★ same condition
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

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-asn11ser (accessed [today's date]).

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