Is DYSF p.Asp427= (c.1281C>T) pathogenic?

DYSF p.Asp427= (c.1281C>T) is classified Conflicting classifications of pathogenicity in DYSF (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-14). Ultra-rare (popmax 0.0165%, mid); Associated with Miyoshi muscular dystrophy 1.

What condition is associated with DYSF p.Asp427= (c.1281C>T)?

DYSF p.Asp427= (c.1281C>T) is associated with Miyoshi muscular dystrophy 1, neuromuscular disease caused by qualitative or quantitative defects of dysferlin (ClinVar).

How common is DYSF p.Asp427= (c.1281C>T) in the general population?

DYSF p.Asp427= (c.1281C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

How is Miyoshi myopathy inherited?

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

DYSF p.Asp427=

c.1281C>T · rs147244033 · VCV499084

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Miyoshi muscular dystrophy 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.9	GERP -4.3
Overall
CADD	5.986	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.0092% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00721%

Overall 0.00266% 43/1,613,596 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
African / African-American	0.016%	6,253
Remaining individualsnot grpmax-eligible	0.008%	12,498
Admixed American	0.00334%	29,978
European (non-Finnish)	0.00195%	51,296

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DYSF
Protein: p.Asp427=
Coding: c.1281C>T
MANE Select: NM_001130987
dbSNP: rs147244033
Type: single nucleotide variant
Location: chr2:71528302 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 427: a β-strand; the c2 3 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: neuromuscular disease caused by qualitative or quantitative defects of dysferlin

For Miyoshi myopathy (Orphanet):

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

Similar variants

DYSF p.Asp427Ala Uncertain significance ★★ ⚠ same residue
DYSF c.1003-3C>A Pathogenic ★★★ same condition
DYSF c.1033+1G>A Pathogenic ★★★ same condition
DYSF c.1033+4A>T Likely pathogenic ★★★ same condition
DYSF c.1149+1G>A Pathogenic ★★★ same condition
DYSF c.1149+1G>C Pathogenic ★★★ same condition
DYSF c.1149+4A>G Pathogenic ★★★ same condition
DYSF c.1276+5G>A 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-asp427 (accessed [today's date]).

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