Is DYSF p.Met1601fs (c.4802dup) pathogenic?

DYSF p.Met1601fs (c.4802dup) is classified Pathogenic in DYSF (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-13). Very rare (popmax 0.00934%, afr); Associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin.

What condition is associated with DYSF p.Met1601fs (c.4802dup)?

DYSF p.Met1601fs (c.4802dup) is associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin, autosomal recessive limb-girdle muscular dystrophy type 2B, Miyoshi muscular dystrophy 1 (ClinVar).

How common is DYSF p.Met1601fs (c.4802dup) in the general population?

DYSF p.Met1601fs (c.4802dup) is very rare (popmax 0.00934%, afr) (gnomAD).

DYSF p.Met1601fs

c.4802dup · rs778065845 · VCV286729

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

Conditions

neuromuscular disease caused by qualitative or quantitative defects of dysferlin

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 44 of 56
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.6	GERP -4.3
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00934% African / African-American · 7/74,986 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000434% 7/1,613,996 alleles · very rare

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.Met1601fs
Coding: c.4802dup
MANE Select: NM_001130987
dbSNP: rs778065845
Type: Duplication
Location: chr2:71658923 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 1601: a β-strand; the c2 6 domain

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

Disease context

neuromuscular disease caused by qualitative or quantitative defects of dysferlin — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2B Miyoshi muscular dystrophy 1

Similar variants

DYSF p.Met1601Leu Uncertain significance ★ ⚠ same residue
DYSF p.Met1601Val Uncertain significance ★ ⚠ same residue
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

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-met1601fs (accessed [today's date]).

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