A complex allele with two variants of p.[Arg74Trp;Asp1270Asn] had virtually no effect on the activity of the CFTR channel, while p.[Arg74Trp;Val201Met;Asp1270Asn] caused mild CF in four out of five patients also carrying a Class 1–2 variant in the trans position. This evidence concerns the gene CFTR and cystic fibrosis.