The sequence variant c.2426T>C in exon 20 changes leucine in position 809 to proline (p.Leu809Pro). Studies in transfected cells show that p.Pro809 is inactive, not processed and retained in the ER. p.Leu809 is localized to the interior of the enzyme and 3d-modelling indicates that p.Leu809Pro causes misfolding of the enzyme. This missense mutation is the third most common alpha-mannosidosis associated sequence variant and accounts for approximately 3 % of the reported disease alleles.