Is DES p.Pro419fs (c.1255_1271del) pathogenic?

DES p.Pro419fs (c.12551271del) is classified Pathogenic in DES (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-06-01). Absent from gnomAD; Associated with myofibrillar myopathy 1.

What condition is associated with DES p.Pro419fs (c.1255_1271del)?

DES p.Pro419fs (c.1255_1271del) is associated with myofibrillar myopathy 1 (ClinVar).

How common is DES p.Pro419fs (c.1255_1271del) in the general population?

DES p.Pro419fs (c.1255_1271del) is absent from gnomAD (gnomAD).

How is Desminopathy inherited?

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

DES p.Pro419fs

c.1255_1271del · rs1553603732 · VCV522796

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 0.011	GERP -1.8, phastCons 0.8

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: DES
Protein: p.Pro419fs
Coding: c.1255_1271del
MANE Select: NM_001927
dbSNP: rs1553603732
Type: Deletion
Location: chr2:219423784 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 419: the 'tail' region; a UniProt-annotated variant site (in mfm1; found in a family with myofibrillar myopathy and arrhythmogenic right ventricular cardiomyopathy)

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.Pro419Ser Pathogenic/Likely pathogenic ★★ ⚠ same residue
DES p.Pro419= Conflicting classifications of pathogenicity ★ same residue
DES p.Pro419Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
DES p.Pro419Thr Uncertain significance ★ ⚠ same residue
DES p.Ala134fs Pathogenic/Likely 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-pro419fs (accessed [today's date]).

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