Is DSC2 p.Ser143= (c.429G>C) pathogenic?

DSC2 p.Ser143= (c.429G>C) is classified Conflicting classifications of pathogenicity in DSC2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-03). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with DSC2 p.Ser143= (c.429G>C)?

DSC2 p.Ser143= (c.429G>C) is associated with Cardiovascular phenotype, arrhythmogenic right ventricular dysplasia 11 (ClinVar).

How common is DSC2 p.Ser143= (c.429G>C) in the general population?

DSC2 p.Ser143= (c.429G>C) is absent from gnomAD v4.1 (gnomAD).

DSC2 p.Ser143=

c.429G>C · rs542638302 · VCV416267

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.3	GERP -4
Overall
CADD	0.868	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DSC2
Protein: p.Ser143=
Coding: c.429G>C
MANE Select: NM_024422
dbSNP: rs542638302
Type: single nucleotide variant
Location: chr18:31091073 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 77.26 · 3 PDB
Residue 143: a β-strand; the cadherin 1 domain

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: arrhythmogenic right ventricular dysplasia 11

Similar variants

DSC2 p.Ser143Leu Uncertain significance ★★ ⚠ same residue
DSC2 p.Ser143Trp Uncertain significance ★ ⚠ 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-ser143 (accessed [today's date]).

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