Is DSG2 p.Phe531= (c.1593C>T) pathogenic?

DSG2 p.Phe531= (c.1593C>T) is classified Likely benign in DSG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-11). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with DSG2 p.Phe531= (c.1593C>T)?

DSG2 p.Phe531= (c.1593C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is DSG2 p.Phe531= (c.1593C>T) in the general population?

DSG2 p.Phe531= (c.1593C>T) is absent from gnomAD v4.1 (gnomAD).

DSG2 p.Phe531=

c.1593C>T · rs2510917959 · VCV2563308

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.083	GERP 1.8, phastCons 0.71
Overall
CADD	5.933	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.Phe531=
Coding: c.1593C>T
MANE Select: NM_001943
dbSNP: rs2510917959
Type: single nucleotide variant
Location: chr18:31536371 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 65.27 · 12 PDB
Residue 531: a UniProt-annotated variant site (in arvd10; likely pathogenic)

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.Phe531Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
DSG2 p.Phe531Leu Uncertain significance ★ ⚠ same residue
DSG2 p.Phe531Ser Uncertain significance ★ ⚠ same residue
DSG2 p.Arg46Trp Pathogenic/Likely pathogenic ★★ same condition
DSG2 p.Asn266Ser Likely pathogenic ★★ same condition
DSG2 p.Gln873Ter Pathogenic/Likely pathogenic ★★ same condition
DSG2 p.Ser404Ter Pathogenic/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-phe531 (accessed [today's date]).

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