Dysferlinopathies are a group of autosomal recessive muscular dystrophies, caused by bi-allelic loss-of-function variants in the gene encoding dysferlin (DYSF). They are characterised by slowly progressive, mid-late onset weakness and atrophy of proximal and/or distal muscles of the limb girdles. Dysferlinopathies are clinically heterogeneous, however, two main presentations are widely recognised: Limb Girdle Muscular Dystrophy 2B and Miyoshi Myopathy. Although there are a few exceptional cases of symptomatic DYSF variant carriers, an autosomal dominant inheritance pattern has not been previously described. Here, we report a large family with a dominantly inherited hyperCKemia and late-onset muscular dystrophy. Genetic analysis identified a segregating heterozygous DYSF frameshifting variant [NM_003494.3:c.6207del p.(Tyr2070fs*3)], absent both in databases of known disease-causing DYSF variants and unaffected control populations. No secondary variants in DYSF or other dystrophy-related genes were identified on whole genome sequencing analysis of the proband’s DNA. Clinical presentations were milder and later onset than typical dysferlinopathy; signs of muscle weakness and atrophy manifested in only three individuals, all in mid-late adulthood. All individuals with the c.6207del variant had elevated serum creatine kinase levels. Histological analysis of muscle biopsy from carriers across three generations showed variable dystrophic signs, including inflammatory infiltrate, regenerating fibres, cores, and myonecrosis. Muscle magnetic resonance imaging showed fatty replacement of tissue in two carriers. Western blot and immunohistochemical analysis of patient muscle biopsy demonstrated consistent reduction of dysferlin, supporting a diagnosis of dysferlinopathy. Allele-specific quantitative PCR analysis of DYSF mRNA from patient muscle biopsy confirmed that the frameshift variant, localised to the extreme C-terminus of dysferlin, is expressed and escapes post-transcriptional mRNA decay. With the identification of this novel family, we propose that autosomal dominant forms of dysferlinopathy may be underappreciated and that some reported cases with mono-allelic DYSF variants may represent dominant dysferlinopathy.