Is DYSF p.Asn1342= (c.4026C>T) pathogenic?

DYSF p.Asn1342= (c.4026C>T) is classified Benign/Likely benign in DYSF (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-04). Common (popmax 48.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Miyoshi muscular dystrophy 1.

How is Miyoshi myopathy inherited?

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

DYSF p.Asn1342=

Q: What condition is associated with DYSF p.Asn1342= (c.4026C>T)?

DYSF p.Asn1342= (c.4026C>T) is associated with Miyoshi muscular dystrophy 1, autosomal recessive limb-girdle muscular dystrophy type 2B, neuromuscular disease caused by qualitative or quantitative defects of dysferlin (ClinVar).

Q: How common is DYSF p.Asn1342= (c.4026C>T) in the general population?

DYSF p.Asn1342= (c.4026C>T) is common (popmax 48.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4026C>T · rs11558179 · VCV94314

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Common

common (popmax 48.4%, afr) — too common for a highly-penetrant pathogenic allele

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 1.1	GERP -4.3, phastCons 1
Overall
CADD	9.162	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 48.4% African / African-American · 36,297/74,922 alleles

Filtering AF 48% ClinGen BA1/BS1 input FAF95, joint · FAF99 47.9%

Overall 7.52% 121,393/1,613,634 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	48.4%	2
Admixed American	10%	10
Middle Eastern	8.41%	12
Ashkenazi Jewishnot grpmax-eligible	8.35%	12
Remaining individualsnot grpmax-eligible	8.31%	12
Amishnot grpmax-eligible	7.35%	14
South Asian	5.38%	19
European (non-Finnish)	5.16%	19
Finnishnot grpmax-eligible	4.8%	21
East Asian	4.59%	22

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.Asn1342=
Coding: c.4026C>T
MANE Select: NM_001130987
dbSNP: rs11558179
Type: single nucleotide variant
Location: chr2:71611313 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 1342: a β-strand; the c2 5 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 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.Asn1342Thr 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-asn1342 (accessed [today's date]).

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