Is DSC2 p.Lys91fs (c.271_272insCAAT) pathogenic?

DSC2 p.Lys91fs (c.271272insCAAT) is classified Pathogenic in DSC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-27). Absent from gnomAD; Associated with Cardiovascular phenotype.

What condition is associated with DSC2 p.Lys91fs (c.271_272insCAAT)?

DSC2 p.Lys91fs (c.271_272insCAAT) is associated with Cardiovascular phenotype (ClinVar).

How common is DSC2 p.Lys91fs (c.271_272insCAAT) in the general population?

DSC2 p.Lys91fs (c.271_272insCAAT) is absent from gnomAD (gnomAD).

DSC2 p.Lys91fs

c.271_272insCAAT · rs2510956114 · VCV3227845

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Cardiovascular phenotype

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 3 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.5	GERP -1.1, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DSC2
Protein: p.Lys91fs
Coding: c.271_272insCAAT
MANE Select: NM_024422
dbSNP: rs2510956114
Type: Insertion
Location: chr18:31092183 (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

Similar variants

DSC2 p.Lys91Glu Uncertain significance ★ ⚠ same residue
DSC2 c.1521-1G>A Likely pathogenic ★★ same condition
DSC2 c.354+2T>A Likely pathogenic ★★ same condition
DSC2 p.Gln620Ter Pathogenic ★★ same condition
DSC2 p.Leu229fs Pathogenic ★★ same condition
DSC2 p.Leu396fs Pathogenic ★★ same condition
DSC2 p.Pro228_Leu229insTer Pathogenic ★★ same condition
DSC2 p.Tyr196fs 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-lys91fs (accessed [today's date]).

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