Is DSG2 p.Pro205= (c.615T>C) pathogenic?

DSG2 p.Pro205= (c.615T>C) is classified Likely benign in DSG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-30). Very rare (popmax 8.48e-05%, nfe); Associated with cardiomyopathy.

What condition is associated with DSG2 p.Pro205= (c.615T>C)?

DSG2 p.Pro205= (c.615T>C) is associated with cardiomyopathy (ClinVar).

How common is DSG2 p.Pro205= (c.615T>C) in the general population?

DSG2 p.Pro205= (c.615T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

DSG2 p.Pro205=

c.615T>C · rs1598811341 · VCV1332050

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

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 -0.41	GERP -2.8
Overall
CADD	8.853	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,792 alleles

Overall 0.000137% 2/1,461,542 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	64,032
European (non-Finnish)grpmax	8.48e-05%	1,179,792

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro205=
Coding: c.615T>C
MANE Select: NM_001943
dbSNP: rs1598811341
Type: single nucleotide variant
Location: chr18:31522174 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 65.27 · 12 PDB
Residue 205: the cadherin 2 domain; a β-strand

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

Disease context

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

Similar variants

DSG2 p.Pro205Leu Uncertain significance ★★ ⚠ same residue
DSG2 p.Pro205Ser Uncertain significance ★★ ⚠ same residue
DSG2 p.Arg46Gln Pathogenic/Likely pathogenic ★★ same condition
DSG2 p.Arg46Trp Pathogenic/Likely pathogenic ★★ same condition
DSG2 p.Tyr783Ter Pathogenic/Likely pathogenic ★★ same condition
DSG2 c.1014+5G>T Uncertain significance ★★ same condition
DSG2 c.216+3A>C Uncertain significance ★★ same condition
DSG2 c.45+5G>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-pro205 (accessed [today's date]).

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