Germ line predisposition disorders analyzed in the review series in the current issue of Blood. The phenotype may be highly variable, even within the same family; in some subjects, it may be absent or very mild, going unnoticed. Of note, patients with DDX41-associated susceptibility to myeloid malignancies have no phenotype before the development of a hematologic malignancy, which typically occurs in the sixth and seventh decades of life; that is, at an age when sporadic hematologic malignancies (not associated with any predisposition disorder) occur.