Abstract: The present invention relates to the field of transgenic animals. More specifically, the present invention provides methods and composition related to humanized transgenic single polymorphism non-human animal systems. In one embodiment, a system comprises (a) a transgenic non-human animal comprising a transgene encoding a wildtype human protein, wherein the protein is biologically active in the animal; and (b) at least one transgenic non-human animal comprising a transgene encoding a variant human protein, wherein the protein is biologically active in the animal and wherein the variant comprises one or more single nucleotide polymorphisms (SNPs).