Is DSG2 p.Gly91= (c.273A>G) pathogenic?

DSG2 p.Gly91= (c.273A>G) is classified Likely benign in DSG2 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-14). Rare (popmax 0.112%, sas); Associated with Cardiovascular phenotype.

What condition is associated with DSG2 p.Gly91= (c.273A>G)?

DSG2 p.Gly91= (c.273A>G) is associated with Cardiovascular phenotype, cardiomyopathy, arrhythmogenic right ventricular dysplasia 10 (ClinVar).

How common is DSG2 p.Gly91= (c.273A>G) in the general population?

DSG2 p.Gly91= (c.273A>G) is rare (popmax 0.112%, sas) (gnomAD).

DSG2 p.Gly91=

c.273A>G · rs376944801 · VCV263740

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

rare (popmax 0.112%, sas)

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 0.54	phastCons 0.89
Overall
CADD	8.438	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.112% South Asian · 102/91,066 alleles

Filtering AF 0.0944% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0878%

Overall 0.0156% 251/1,613,770 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.112%	893
Ashkenazi Jewishnot grpmax-eligible	0.0608%	1,644
Middle Eastern	0.033%	3,030
Remaining individualsnot grpmax-eligible	0.0192%	5,207
European (non-Finnish)	0.00958%	10,440
African / African-American	0.004%	25,012
Admixed American	0.00167%	60,010

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.Gly91=
Coding: c.273A>G
MANE Select: NM_001943
dbSNP: rs376944801
Type: single nucleotide variant
Location: chr18:31520859 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 65.27 · 12 PDB
Residue 91: the cadherin 1 domain; a β-strand

Full DSG2 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 10 arrhythmogenic right ventricular cardiomyopathy

Similar variants

DSG2 p.Gly91Arg Uncertain significance ★★ ⚠ same residue
DSG2 c.1423+1G>T Likely pathogenic ★★ same condition
DSG2 c.1424-1G>A Likely pathogenic ★★ same condition
DSG2 c.523+1G>T Pathogenic/Likely pathogenic ★★ same condition
DSG2 c.690+1G>A Pathogenic ★★ same condition
DSG2 c.81+1G>T Likely pathogenic ★★ same condition
DSG2 c.829-2A>T Likely pathogenic ★★ same condition
DSG2 p.Arg46Gln Pathogenic/Likely 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/dsg2-p-gly91 (accessed [today's date]).

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