Is DES p.Ser68fs (c.197dup) pathogenic?

DES p.Ser68fs (c.197dup) is classified Pathogenic in DES (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-25). Associated with myofibrillar myopathy 1.

What condition is associated with DES p.Ser68fs (c.197dup)?

DES p.Ser68fs (c.197dup) is associated with myofibrillar myopathy 1 (ClinVar).

How is Desminopathy inherited?

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

DES p.Ser68fs

c.197dup · VCV4790052

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

myofibrillar myopathy 1

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 1 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.6	GERP -0.59, phastCons 0.9
Region caveats
Repeat context	tandem	G-rich low complexity · ambiguous alignment · confidence, not pathogenicity

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

Variant & gene context

Gene: DES
Protein: p.Ser68fs
Coding: c.197dup
MANE Select: NM_001927
Type: Duplication
Location: chr2:219418658 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 68: a modified residue (phosphoserine); the 'head' region

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

Disease context

myofibrillar myopathy 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Desminopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy

Similar variants

DES p.Ser68= Likely benign ★★ same residue
DES p.Ser68_Leu69= Conflicting classifications of pathogenicity ★ same residue
DES p.Leu66fs Pathogenic/Likely pathogenic ★★ same condition
DES c.1023+6_1023+24dup Uncertain significance ★★ same condition
DES c.1371+2dup Uncertain significance ★★ same condition
DES p.Asp343_Ser344dup Likely pathogenic ★ same condition
DES p.Gln316fs Likely pathogenic ★ same condition
DES p.Gly41fs 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/des-p-ser68fs (accessed [today's date]).

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