Is DSC2 p.Arg279fs (c.834_835dup) pathogenic?

DSC2 p.Arg279fs (c.834835dup) is classified Likely pathogenic in DSC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-01). Very rare (popmax 0.000169%, nfe).

How common is DSC2 p.Arg279fs (c.834_835dup) in the general population?

DSC2 p.Arg279fs (c.834_835dup) is very rare (popmax 0.000169%, nfe) (gnomAD).

DSC2 p.Arg279fs

c.834_835dup · rs2510951321 · VCV3027249

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

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 7 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.41	GERP 0.28, phastCons 0.023

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,022 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,842 alleles · very rare

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.Arg279fs
Coding: c.834_835dup
MANE Select: NM_024422
dbSNP: rs2510951321
Type: Microsatellite
Location: chr18:31086682 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 77.26 · 3 PDB
Residue 279: the cadherin 2 domain

Full DSC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DSC2 p.Arg279His Uncertain significance ★★ ⚠ same residue
DSC2 p.Arg279Leu Uncertain significance ★★ ⚠ same residue
DSC2 p.Arg279Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
DSC3 p.Arg279Cys Uncertain significance ★ ⚠ same residue
DSC2 c.2509-111_2509-110del Uncertain significance ★★ same type
DSC2 p.Asn546del Uncertain significance ★★ same type
DSC2 p.Glu463del Uncertain significance ★★ same type
DSC2 p.Gly863fs Uncertain significance ★★ same type

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-arg279fs (accessed [today's date]).

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