Is DYSF p.Arg1853fs (c.5557del) pathogenic?

DYSF p.Arg1853fs (c.5557del) is classified Pathogenic in DYSF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-07). Associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin.

DYSF p.Arg1853fs

Q: What condition is associated with DYSF p.Arg1853fs (c.5557del)?

DYSF p.Arg1853fs (c.5557del) is associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin (ClinVar).

c.5557del · VCV3649102

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 50 of 56
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.6	GERP -1.3, phastCons 1

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

Variant & gene context

Gene: DYSF
Protein: p.Arg1853fs
Coding: c.5557del
MANE Select: NM_001130987
Type: Deletion
Location: chr2:71669122 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 1853: the c2 7 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

Similar variants

DYSF p.Arg1853Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
DYSF p.Arg1853His Conflicting classifications of pathogenicity ★ ⚠ same residue
DYSF p.Arg1853= Likely benign ★ same residue
DYSF c.951+1del Pathogenic ★★★ same condition
DYSF p.Ala927Leufs Pathogenic ★★★ same condition
DYSF p.Asp1181fs Pathogenic ★★★ same condition
DYSF p.Asp1255fs Pathogenic ★★★ same condition
DYSF p.Gln1985fs 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-arg1853fs (accessed [today's date]).

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