Is DES p.Ile420fs (c.1257del) pathogenic?

DES p.Ile420fs (c.1257del) is classified Pathogenic in DES (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-18). Associated with myofibrillar myopathy 1.

What condition is associated with DES p.Ile420fs (c.1257del)?

DES p.Ile420fs (c.1257del) 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.Ile420fs

c.1257del · VCV4786122

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 7 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1

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

Variant & gene context

Gene: DES
Protein: p.Ile420fs
Coding: c.1257del
MANE Select: NM_001927
Type: Deletion
Location: chr2:219423786 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 420: the 'tail' 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.Ile420Leu Uncertain significance ★★ ⚠ same residue
DES p.Ile420= Likely benign ★★ same residue
DES p.Ile420Thr Uncertain significance ★ same residue
DES p.Ala134fs Pathogenic/Likely pathogenic ★★ same condition
DES p.Pro419fs Pathogenic ★★ same condition
DES p.Thr76fs Pathogenic/Likely pathogenic ★★ same condition
DES p.Tyr405fs Pathogenic ★★ same condition
DES p.Glu179_Leu184del Uncertain significance ★★ 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-ile420fs (accessed [today's date]).

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