DES (Desmin) variants and mutations

DES (also known as Desmin) is a human protein-coding gene encoding a desmin protein. Its desmin filaments mechanically integrate sarcomeres with the nucleus, mitochondria, and cell junctions in striated muscle. Pathogenic variants cause desmin-related myopathy and can produce cardiomyopathy, conduction disease, and skeletal-muscle weakness. This analysis covers 1,292 DES variants and mutations. Of these, 10% have pathogenic or likely pathogenic clinical classifications, 89% have computational variant effect predictions from REVEL and MutPred, and 50% have population-specific frequency data. Disease context includes myofibrillar myopathy 1, Desminopathy, and dilated cardiomyopathy 1I. Example DES variants include M1T, M1V, and S2I.

Variant analysis overview

Gene: DES
Protein: Desmin
UniProt accession: P17661
Organism: Homo sapiens
Variants analyzed: 1292
Variant scope: all variants
Completed: 2026-08-10

Variant and mutation evidence

Variant composition: 869 unspecified-consequence records; 218 missense variants; 153 synonymous variants; 5 in-frame deletions; 26 frameshift variants; 15 stop-gained variants; 1 in-frame insertions; 5 substitution
Clinical classifications: 133 pathogenic or likely pathogenic; 40 benign or likely benign; 515 uncertain-significance; 53 other clinical labels.
Computational signals: 289 REVEL high-risk; 119 MutPred high-risk.
Variant classes: 1,061 missense; 153 synonymous; 74 truncating or splice.
Prediction scores: 1,145 variants have prediction scores (89% of the analyzed set).
Literature: 40 publications are represented in the literature summary.

Clinical, disease, and population context

Clinical evidence: 22 records have expert-only or criteria-backed evidence.
Clinical annotations: 744 variants have clinical annotations.
Population evidence: 979 variants have population-frequency evidence.
Disease context: 25 disease associations are represented. Top associations: myofibrillar myopathy 1, Desminopathy, dilated cardiomyopathy 1I, neurogenic scapuloperoneal syndrome, Kaeser type, Autosomal recessive limb-girdle muscular dystrophy due to desmin deficiency, Scapuloperoneal amyotrophy, dilated cardiomyopathy, cardiomyopathy, Abnormality of the cardiovascular system, arrhythmogenic right ventricular cardiomyopathy, familial dilated cardiomyopathy, MFM1.

Protein structure and variant hotspots

Protein features: 1 domains; 21 post-translational modification sites.
Ancestry evidence: 642 variants have ancestry-specific frequency data.
Structural context: 736 variants have structural context.
PTM context: 70 variants overlap post-translational modification sites.
3D hotspots: 3 hotspot clusters were identified. Clusters at residues 74-80 (tolerant, 18 variants); residues 117-127 (intolerant, 16 variants); residues 167-181 (intolerant, 22 variants).
Allosteric analysis: 1 functional sites were identified.
gnomAD gene constraint: pLI 0.00 (tolerant of loss-of-function variation); LOEUF 0.62; missense Z-score 0.84.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable DES variants

Examples include M1T, M1V, S2I, S2N, S2S, S2R, Q3*, Q3E. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

DES analysis run — DES (1,292 variants) — completed 2026-08-10