Is DSG2 p.Phe388fs (c.1164del) pathogenic?

DSG2 p.Phe388fs (c.1164del) is classified Pathogenic in DSG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-17). Associated with Cardiovascular phenotype.

What condition is associated with DSG2 p.Phe388fs (c.1164del)?

DSG2 p.Phe388fs (c.1164del) is associated with Cardiovascular phenotype (ClinVar).

DSG2 p.Phe388fs

c.1164del · VCV3505432

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.43	GERP -2.1

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

Variant & gene context

Gene: DSG2
Protein: p.Phe388fs
Coding: c.1164del
MANE Select: NM_001943
Type: Deletion
Location: chr18:31531133 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 65.27 · 12 PDB
Residue 388: the cadherin 3 domain

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

Similar variants

DSG2 p.Phe388Cys Uncertain significance ★★ ⚠ same residue
DSG2 p.Phe388= Likely benign ★★ same residue
DSG2 c.828_828+2del Uncertain significance ★★ same condition
DSG2 p.Arg1049fs Uncertain significance ★★ same condition
DSG2 p.Leu15del Uncertain significance ★★ same condition
DSG2 p.Ala764fs Likely pathogenic ★ same condition
DSG2 p.Asp162fs Pathogenic ★ same condition
DSG2 p.Leu150fs 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-phe388fs (accessed [today's date]).

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