Is DSC2 p.Pro69= (c.207T>C) pathogenic?

DSC2 p.Pro69= (c.207T>C) is classified Likely benign in DSC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-11). Absent from gnomAD v4.1; Associated with cardiomyopathy.

What condition is associated with DSC2 p.Pro69= (c.207T>C)?

DSC2 p.Pro69= (c.207T>C) is associated with cardiomyopathy (ClinVar).

How common is DSC2 p.Pro69= (c.207T>C) in the general population?

DSC2 p.Pro69= (c.207T>C) is absent from gnomAD v4.1 (gnomAD).

DSC2 p.Pro69=

c.207T>C · rs2144846907 · VCV1172138

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.071	GERP -4, phastCons 0.046
Overall
CADD	7.94	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: DSC2
Protein: p.Pro69=
Coding: c.207T>C
MANE Select: NM_024422
dbSNP: rs2144846907
Type: single nucleotide variant
Location: chr18:31092248 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 77.26 · 3 PDB

Full DSC2 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

DSC2 p.Pro69Ser Uncertain significance ★★ ⚠ same residue
DSC2 p.Pro69Thr Uncertain significance ★ ⚠ same residue
DSC2 c.1077+2T>G Uncertain significance ★★ same condition
DSC2 c.1520+4C>T Uncertain significance ★★ same condition
DSC2 c.942+3A>G Uncertain significance ★★ same condition
DSC2 c.942+6A>G Uncertain significance ★★ same condition
DSC2 p.Ala138Ser Uncertain significance ★★ ⚠ same condition
DSC2 p.Ala213Val 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/dsc2-p-pro69 (accessed [today's date]).

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