Is DYSF p.Asp21fs (c.60_61dup) pathogenic?

DYSF p.Asp21fs (c.6061dup) is classified Likely pathogenic in DYSF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-16). Associated with Miyoshi muscular dystrophy 1.

What condition is associated with DYSF p.Asp21fs (c.60_61dup)?

DYSF p.Asp21fs (c.60_61dup) is associated with Miyoshi muscular dystrophy 1, autosomal recessive limb-girdle muscular dystrophy type 2B, distal myopathy with anterior tibial onset (ClinVar).

How is Miyoshi myopathy inherited?

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

DYSF p.Asp21fs

c.60_61dup · VCV3586906

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Miyoshi muscular dystrophy 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-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.2	GERP 1.5, phastCons 1

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

Variant & gene context

Gene: DYSF
Protein: p.Asp21fs
Coding: c.60_61dup
MANE Select: NM_001130987 · reported on NM_003494
Type: Duplication
Location: chr2:71454056 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 21: a binding site; the c2 1 domain

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

Disease context

Miyoshi muscular dystrophy 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2B distal myopathy with anterior tibial onset

For Miyoshi myopathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult
Prevalence: 1-9 / 1 000 000 (Japan)

Similar variants

DYSF c.1267_1276+4dup Pathogenic ★★★ same condition
DYSF c.1274_1276+4dup Likely pathogenic ★★★ same condition
DYSF c.1493+2dup Pathogenic ★★★ same condition
DYSF p.Asn44fs Pathogenic ★★★ same condition
DYSF p.Asp320fs Pathogenic ★★★ same condition
DYSF p.Asp497fs Pathogenic ★★★ same condition
DYSF p.Glu2033fs Pathogenic ★★★ same condition
DYSF p.Ile1036Hisfs 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/dysf-p-asp21fs (accessed [today's date]).

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