Is DES p.Ser424fs (c.1268_1269insT) pathogenic?

DES p.Ser424fs (c.12681269insT) is classified Likely pathogenic in DES (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-02). Associated with dilated cardiomyopathy 1I.

What condition is associated with DES p.Ser424fs (c.1268_1269insT)?

DES p.Ser424fs (c.1268_1269insT) is associated with dilated cardiomyopathy 1I, myofibrillar myopathy 1 (ClinVar).

How is Familial isolated dilated cardiomyopathy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DES p.Ser424fs

c.1268_1269insT · VCV3779567

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

dilated cardiomyopathy 1I

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 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2	GERP -2, phastCons 1

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

Variant & gene context

Gene: DES
Protein: p.Ser424fs
Coding: c.1268_1269insT
MANE Select: NM_001927
Type: Insertion
Location: chr2:219423800 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 424: the 'tail' region; a modified residue (phosphoserine)

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

Disease context

dilated cardiomyopathy 1I — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: myofibrillar myopathy 1

For Familial isolated dilated cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

DES p.Ser424= Likely benign ★★ same residue
DES p.Gly86fs Pathogenic/Likely pathogenic ★★ same condition
DES p.Gly27_Leu30dup Uncertain significance ★★ same condition
DES p.Leu190fs Pathogenic ★ same condition
DES p.Met447fs Pathogenic ★ same condition
DES p.Tyr423fs Likely pathogenic ★ same condition
DES p.Ser424Ala Uncertain significance ★ ⚠ same residue
DES p.Ser424Phe Uncertain significance ★ ⚠ same residue

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/des-p-ser424fs (accessed [today's date]).

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