The invention provides a prokaryotic phenylalanine ammonia-lyase (PAL) variant, wherein said PAL variant has a greater phenylalanine-converting activity and/or a reduced immunogenicity as compared to a wild-type PAL as well as a pharmaceutical composition comprising same. Further provided is the use of the PAL variant for treating a disease in a subject caused all or in part by a deficiency in phenylalanine hydroxylase (PAH), for treating classic severe PKU in a subject or an infant of between 0 and 3 years having PKU, or for treating a pregnant female having hyperphenylalaninemia (HPA), wherein the PAL variant is administered in combination with a protein-restricted diet.
