The sequence variant c.2248C>T in exon 18 changes arginine in position 750 to tryptophan (p.Arg750Trp). Studies in transfected cells show that p.Trp750 is inactive, not processed and retained in the ER. p.Arg750 is localized to the domain interface, and 3d-modelling indicates that the substitution causes misfolding of the enzyme. This missense mutation is the most common alpha-mannosidosis associated sequence variant and accounts for approximately 28 % of the reported disease alleles.