Is DSG2 p.Glu384Ter (c.1150G>T) pathogenic?

DSG2 p.Glu384Ter (c.1150G>T) is classified Likely pathogenic in DSG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-22). Very rare (popmax 0.0022%, sas); Associated with DSG2-related disorders.

What condition is associated with DSG2 p.Glu384Ter (c.1150G>T)?

DSG2 p.Glu384Ter (c.1150G>T) is associated with DSG2-related disorders, dilated cardiomyopathy 1BB (ClinVar).

How common is DSG2 p.Glu384Ter (c.1150G>T) in the general population?

DSG2 p.Glu384Ter (c.1150G>T) is very rare (popmax 0.0022%, sas) (gnomAD).

DSG2 p.Glu384Ter

c.1150G>T · VCV4852856

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

DSG2-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 15
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,078 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000186% 3/1,613,996 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,539
European (non-Finnish)	8.47e-05%	1,180,022

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.Glu384Ter
Coding: c.1150G>T
MANE Select: NM_001943
Type: single nucleotide variant
Location: chr18:31531122 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 65.27 · 12 PDB
Residue 384: the 'interacts with human adenovirus b3 fiber protein' region; the cadherin 3 domain

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

Disease context

DSG2-related disorders

Also linked: dilated cardiomyopathy 1BB

Similar variants

DSG2 p.Glu384Ala Uncertain significance ★ ⚠ same residue
DSG2 p.Glu384Asp Uncertain significance ★ ⚠ same residue
DSG2 p.Glu384Gly Uncertain significance ★ ⚠ same residue
DSG2 c.1423+1G>T Likely pathogenic ★★ same condition
DSG2 p.Arg46Gln Pathogenic/Likely pathogenic ★★ same condition
DSG2 p.Arg49His Pathogenic/Likely pathogenic ★★ same condition
DSG2 p.Gln916Ter Likely pathogenic ★★ same condition
DSG2 c.216+3A>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-glu384ter (accessed [today's date]).

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