Pathogenic variants of ACAN have been reported to cause spondyloepiphyseal dysplasia Kimberley type, spondyloepimetaphyseal dysplasia, familial osteochondritis dissecans and idiopathic short stature with normal to advanced bone age.
A mutation in the variable repeat region of the aggrecan gene (AGC1) causes a form of spondyloepiphyseal dysplasia associated with severe, premature osteoarthritis.