DYSF p.Phe1128fs
c.3381_3382del · rs398123780 · VCV94303
ClinGen expert panel — Limb Girdle Muscular Dystrophy VCEP
Pathogenic for limb-girdle muscular dystrophy. Applied ACMG criteria (verbatim):
PVS1 PM3_Supporting PM2_Supporting PP4
Curation rationale (ClinGen, verbatim)
The NM_003494.4: c.3327_3328del p.(Phe1110CysfsTer3) variant in DYSF, which is also known as NM_001130987.2: c.3381_3382del p.(Phe1128CysfsTer3), is a frameshift variant that is predicted to result in a premature stop codon in exon 30/55, leading to nonsense mediated decay in a gene in which loss of function is an established mechanism of disease (PVS1). This variant has been reported in at least two unrelated patients with clinical signs of LGMD (PMID: 35723113, 34559919), including in unconfirmed phase with a pathogenic variant (NM_003494.4: c.965T>C p.(Leu322Pro), PMID: 34559919, 0.5 pts) (PM3_Supporting). At least one patient with this variant and a second presumed diagnostic DYSF variant displayed progressive limb girdle muscle weakness (PMID: 34559919; PP4). This variant is also absent from gnomAD v4.1.0 (PM2_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen LGMD VCEP specifications version 2.0.0; 02/10/2026): PVS1, PM3_Supporting, PP4, PM2_Supporting.
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
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 30 of 56 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 2.1, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
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.Phe1128fs
- Coding
- c.3381_3382del
- MANE Select
- NM_001130987
- dbSNP
- rs398123780
- Type
- Microsatellite
- Location
- chr2:71574347 (GRCh38)
- Gene constraint
- LOEUF 0.836 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.25 · 11 PDB
Similar variants
- DYSF p.Met1128Ilefs Pathogenic/Likely pathogenic ★★ same residue
- DYSF p.Leu1092fs Pathogenic ★★★ same condition
- DYSF p.Ser1939fs Pathogenic ★★★ same condition
- DYSF p.1080AE[3] Benign ★★★ same condition
- DYSF p.Leu298fs Pathogenic ★★ same condition
- DYSF p.Ser1189fs Pathogenic ★★ same condition
- DYSF p.2087ILFI[1] Uncertain significance ★★ same condition
- DYSF p.His1055fs 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-phe1128fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown