Using NLRP3-deficient U937 cells reconstituted with doxycycline-inducible NLRP3 variants in response to NLRP3 induction, the present inventors have developed a novel functional cell-based assay to screen for NLRP3 variants that uncouples NLRP3 induction, priming and activation. The inventors studied and characterized 38 NLRP3 variants by assessing pyroptosis and IL-1β/18 secretion in, priming and/or activation. The results were confirmed in primary monocytes from patients carrying different variants. The present invention pertains to a method for characterizing NLRP3 mutations that allows discriminating gain-of-function mutants from polymorphism without any impact on NLRP3 activity. The invention also relates to methods for the diagnosis of NLRP3-associated autoinflammatory diseases and for predicting a response to NLRP3 inhibitors based on the detection of specific NLRP3 mutations in a sample obtained from a patient. The invention also relates to new NLRP3 inhibitors.