Is DSG2 p.Pro994= (c.2982T>C) pathogenic?

DSG2 p.Pro994= (c.2982T>C) is classified Likely benign in DSG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-16). Absent from gnomAD v4.1; Associated with cardiomyopathy.

What condition is associated with DSG2 p.Pro994= (c.2982T>C)?

DSG2 p.Pro994= (c.2982T>C) is associated with cardiomyopathy (ClinVar).

How common is DSG2 p.Pro994= (c.2982T>C) in the general population?

DSG2 p.Pro994= (c.2982T>C) is absent from gnomAD v4.1 (gnomAD).

DSG2 p.Pro994=

c.2982T>C · rs2073310013 · VCV927246

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

cardiomyopathy

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 -1.5
Overall
CADD	4.259	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: DSG2
Protein: p.Pro994=
Coding: c.2982T>C
MANE Select: NM_001943
dbSNP: rs2073310013
Type: single nucleotide variant
Location: chr18:31546368 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 65.27 · 12 PDB
Residue 994: a UniProt-annotated variant site (in arvd10; uncertain significance; evidence of residual myocardium, fibrous tissue, fatty tissue, dysmetric and dysmorphic nuclei and prominent cytoplasmic vacuolization; decreases the number of desmosomes at intercalated disks also increases desmosome gap; smaller intercellular gaps, with repeating couplings, abnormally located desmosomes and pale internal plaques); a UniProt-annotated variant site (in arvd10; uncertain significance)

Full DSG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DSG2 p.Pro994Leu Uncertain significance ★ ⚠ same residue
DSG2 p.Pro994Ser Uncertain significance ★ ⚠ same residue
DSG2 p.Arg46Gln Pathogenic/Likely pathogenic ★★ same condition
DSG2 p.Arg46Trp Pathogenic/Likely pathogenic ★★ same condition
DSG2 p.Tyr783Ter Pathogenic/Likely pathogenic ★★ same condition
DSG2 c.1014+5G>T Uncertain significance ★★ same condition
DSG2 c.216+3A>C Uncertain significance ★★ same condition
DSG2 c.45+5G>C Uncertain significance ★★ 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/dsg2-p-pro994 (accessed [today's date]).

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