CFTR displays substantial allelic heterogeneity with greater than 300 variants reported to be disease-causing1 with some relatively frequent (e.g. the p.Phe508del 3 bp in-frame deletion; 70% of European CF chromosomes) but most spanning the rarer frequency spectrum (e.g. p.Gly551Asp; 2.11% of CF chromosomes according to the Clinical and Functional Translation of CFTR database or CFTR2; https://www.cftr2.org).2 Therefore, CFTR can illustrate what is gained and missed from imputation on a well-studied disease-specific locus to evaluate the relative merits of different imputation designs. This evidence concerns the gene CFTR and cystic fibrosis.