Is DSG2 p.Thr922= (c.2766A>G) pathogenic?

DSG2 p.Thr922= (c.2766A>G) is classified Likely benign in DSG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-03-09). Very rare (popmax 0.000593%, nfe); Associated with arrhythmogenic right ventricular cardiomyopathy.

What condition is associated with DSG2 p.Thr922= (c.2766A>G)?

DSG2 p.Thr922= (c.2766A>G) is associated with arrhythmogenic right ventricular cardiomyopathy, cardiomyopathy (ClinVar).

How common is DSG2 p.Thr922= (c.2766A>G) in the general population?

DSG2 p.Thr922= (c.2766A>G) is very rare (popmax 0.000593%, nfe) (gnomAD).

DSG2 p.Thr922=

c.2766A>G · rs1347885484 · VCV1171879

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Conditions

arrhythmogenic right ventricular 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 -0.64
Overall
CADD	0.902	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000593% European (non-Finnish) · 7/1,180,026 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000479% 7/1,461,888 alleles · very rare

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: DSG2
Protein: p.Thr922=
Coding: c.2766A>G
MANE Select: NM_001943
dbSNP: rs1347885484
Type: single nucleotide variant
Location: chr18:31546152 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 65.27 · 12 PDB
Residue 922: a modified residue (phosphothreonine); 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

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

Also linked: cardiomyopathy

Similar variants

DSG2 p.Thr922fs Conflicting classifications of pathogenicity ★ same residue
DSG2 p.Arg46Gln Pathogenic/Likely pathogenic ★★ same condition
DSG2 p.Arg46Trp Pathogenic/Likely pathogenic ★★ same condition
DSG2 p.Arg49His Pathogenic/Likely pathogenic ★★ same condition
DSG2 p.Ser314Ter Pathogenic/Likely pathogenic ★★ same condition
DSG2 p.Tyr130Ter Likely pathogenic ★★ same condition
DSG2 p.Tyr783Ter Pathogenic/Likely pathogenic ★★ same condition
DSG2 c.1014+5G>T 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-thr922 (accessed [today's date]).

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