The SMAD4 variants G352E [48], G352R [49], R361H, R361L [48], C363R [50], G386D [49], W509R, G510V [50], L533P, L533R [48], and L533V [51] are previously identified in juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, whereas G491V is reported in colorectal cancer [51]. This evidence concerns the gene SMAD4 and juvenile polyposis syndrome.