Is DYSF p.Lys883fs (c.2646_2647del) pathogenic?

DYSF p.Lys883fs (c.26462647del) is classified Likely pathogenic in DYSF (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-30). Absent from gnomAD; Associated with autosomal recessive limb-girdle muscular dystrophy.

What condition is associated with DYSF p.Lys883fs (c.2646_2647del)?

DYSF p.Lys883fs (c.2646_2647del) is associated with autosomal recessive limb-girdle muscular dystrophy (ClinVar).

How common is DYSF p.Lys883fs (c.2646_2647del) in the general population?

DYSF p.Lys883fs (c.2646_2647del) is absent from gnomAD (gnomAD).

DYSF p.Lys883fs

c.2646_2647del · rs2545798157 · VCV1726692

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

autosomal recessive limb-girdle muscular dystrophy

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 25 of 56
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.7	GERP -1.5

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: DYSF
Protein: p.Lys883fs
Coding: c.2646_2647del
MANE Select: NM_001130987
dbSNP: rs2545798157
Type: Microsatellite
Location: chr2:71568029 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 883: a β-strand

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

Disease context

autosomal recessive limb-girdle muscular dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DYSF p.Leu1092fs Pathogenic ★★★ same condition
DYSF p.Ser1939fs Pathogenic ★★★ same condition
DYSF p.Ser1372del Uncertain significance ★★★ same condition
DYSF p.1080AE[3] Benign ★★★ same condition
DYSF p.Lys883= Likely benign ★ 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

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-lys883fs (accessed [today's date]).

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