Is DSC2 p.Leu37= (c.111A>G) pathogenic?

DSC2 p.Leu37= (c.111A>G) is classified Benign in DSC2 (ClinVar, Multiple submitters, 18 submitters; last evaluated 2026-02-04). Common (popmax 17.5%, mid) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with DSC2 p.Leu37= (c.111A>G)?

DSC2 p.Leu37= (c.111A>G) is associated with Cardiovascular phenotype, cardiomyopathy, arrhythmogenic right ventricular dysplasia 11 (ClinVar).

DSC2 p.Leu37=

Q: How common is DSC2 p.Leu37= (c.111A>G) in the general population?

DSC2 p.Leu37= (c.111A>G) is common (popmax 17.5%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.111A>G · rs12954874 · VCV46163

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 18 submitters

gnomAD v4.1

Common

common (popmax 17.5%, mid) — too common for a highly-penetrant pathogenic allele

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 -4.3	GERP -4
Overall
CADD	0.065	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 17.5% Middle Eastern · 1,048/6,000 alleles

Filtering AF 16.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 16.2%

Overall 11.4% 183,167/1,601,644 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	17.5%	6
Admixed American	15.3%	7
Ashkenazi Jewishnot grpmax-eligible	14%	7
South Asian	11.9%	8
Remaining individualsnot grpmax-eligible	11.9%	8
East Asian	11.7%	9
European (non-Finnish)	11.7%	9
African / African-American	7.94%	13
Finnishnot grpmax-eligible	4.08%	24
Amishnot grpmax-eligible	1.65%	61

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: DSC2
Protein: p.Leu37=
Coding: c.111A>G
MANE Select: NM_024422
dbSNP: rs12954874
Type: single nucleotide variant
Location: chr18:31093602 (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

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

Also linked: cardiomyopathy arrhythmogenic right ventricular dysplasia 11 familial isolated arrhythmogenic right ventricular dysplasia

Similar variants

DSC2 p.Leu37Ile Uncertain significance ★ ⚠ same residue
DSC2 p.Leu37fs Pathogenic ★ same residue
DSC3 p.Leu37Pro Uncertain significance ★ ⚠ same residue
DSC2 c.1521-1G>A Likely pathogenic ★★ same condition
DSC2 c.1664-1G>A Likely pathogenic ★★ same condition
DSC2 c.354+2T>A Likely pathogenic ★★ same condition
DSC2 c.355-1G>A Likely pathogenic ★★ same condition
DSC2 p.Gln554Ter 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/dsc2-p-leu37 (accessed [today's date]).

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