Is DSC2 p.Gln287Ter (c.859C>T) pathogenic?

DSC2 p.Gln287Ter (c.859C>T) is classified Likely pathogenic in DSC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-25). Very rare (popmax 0.0011%, sas); Associated with DSC2-related disorder.

What condition is associated with DSC2 p.Gln287Ter (c.859C>T)?

DSC2 p.Gln287Ter (c.859C>T) is associated with DSC2-related disorder (ClinVar).

How common is DSC2 p.Gln287Ter (c.859C>T) in the general population?

DSC2 p.Gln287Ter (c.859C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

DSC2 p.Gln287Ter

c.859C>T · VCV3773844

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

DSC2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 16
Splicing
SpliceAI	Δ0.96	donor gain · deltas
Pangolin	Δ0.83	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Overall
CADD	47.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,074 alleles

Overall 6.84e-05% 1/1,461,846 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.Gln287Ter
Coding: c.859C>T
MANE Select: NM_024422
Type: single nucleotide variant
Location: chr18:31086659 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 77.26 · 3 PDB
Residue 287: a β-strand; the cadherin 2 domain

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

Disease context

DSC2-related disorder

Similar variants

DSC2 p.Gln287Arg Uncertain significance ★★ ⚠ same residue
DSC2 p.Gln287Pro Uncertain significance ★ ⚠ same residue
DSC2 p.Gln554Ter Pathogenic ★★ same condition
DSC2 c.943-2A>G Likely pathogenic ★ same condition
DSC2 p.Arg203Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
DSC2 p.Gln287_Val288delinsHisLeu Uncertain significance ★ same residue
DSG2 p.Thr335Ala Conflicting classifications of pathogenicity ★ ⚠ same condition
DSC2 p.Lys481= Likely benign 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-gln287ter (accessed [today's date]).

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