Is DYSF p.Phe1223fs (c.3667_3673del) pathogenic?

DYSF p.Phe1223fs (c.36673673del) is classified Likely pathogenic in DYSF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-24). Absent from gnomAD; Associated with autosomal recessive limb-girdle muscular dystrophy.

What condition is associated with DYSF p.Phe1223fs (c.3667_3673del)?

DYSF p.Phe1223fs (c.3667_3673del) is associated with autosomal recessive limb-girdle muscular dystrophy (ClinVar).

How common is DYSF p.Phe1223fs (c.3667_3673del) in the general population?

DYSF p.Phe1223fs (c.3667_3673del) is absent from gnomAD (gnomAD).

DYSF p.Phe1223fs

c.3667_3673del · rs2546046409 · VCV1724068

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 33 of 56
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP -0.5, phastCons 1

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.Phe1223fs
Coding: c.3667_3673del
MANE Select: NM_001130987
dbSNP: rs2546046409
Type: Deletion
Location: chr2:71598656 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 1223: an α-helix; the c2 4 domain

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 c.240-159_345+1237del Pathogenic ★★★ same condition
DYSF c.345+1del Pathogenic ★★★ same condition
DYSF c.3756+905_3897+151del Pathogenic ★★★ same condition
DYSF c.5885-51_6063+50del Pathogenic ★★★ same condition
DYSF c.92-1496_239+950del Pathogenic ★★★ same condition
DYSF c.951+1del Pathogenic ★★★ same condition
DYSF p.Ala927Leufs Pathogenic ★★★ same condition
DYSF p.Arg1759fs 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-phe1223fs (accessed [today's date]).

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