A consensus-driven pathogenicity classification was recently proposed to support the urgent need for clear guidelines and uniform diagnosis of FMF across the world.5 An unforeseen outcome of this study was the large number of MEFV variants that were classified as ‘variants of uncertain significance’ or ‘unsolved pathogenicity’, demonstrating the urgent need for insight in the functional impact of these MEFV variants on Pyrin function. This evidence concerns the gene MEFV and familial Mediterranean fever.