Is DSC2 p.Pro290= (c.870A>G) pathogenic?

DSC2 p.Pro290= (c.870A>G) is classified Likely benign in DSC2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.0164%, mid); Associated with Cardiovascular phenotype.

What condition is associated with DSC2 p.Pro290= (c.870A>G)?

DSC2 p.Pro290= (c.870A>G) is associated with Cardiovascular phenotype, cardiomyopathy, arrhythmogenic right ventricular dysplasia 11 (ClinVar).

How common is DSC2 p.Pro290= (c.870A>G) in the general population?

DSC2 p.Pro290= (c.870A>G) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

DSC2 p.Pro290=

c.870A>G · rs142653119 · VCV264606

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

Cardiovascular phenotype

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 -14	GERP -4
Overall
CADD	0.037	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00842% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00787%

Overall 0.0075% 121/1,614,076 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
European (non-Finnish)	0.00991%	10,086
Remaining individualsnot grpmax-eligible	0.0032%	31,243
African / African-American	0.00133%	74,936

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.Pro290=
Coding: c.870A>G
MANE Select: NM_024422
dbSNP: rs142653119
Type: single nucleotide variant
Location: chr18:31086648 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 77.26 · 3 PDB
Residue 290: the cadherin 2 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: cardiomyopathy arrhythmogenic right ventricular dysplasia 11

Similar variants

DSC2 p.Pro290Gln Uncertain significance ★ ⚠ same residue
DSC2 p.Pro290Leu 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-pro290 (accessed [today's date]).

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