AbstractPyrin protein is the product of the MEFV gene, mutations in which cause manifestation of familial Mediterranean fever (FMF). Functions of pyrin are not completely clear. The secondary structure of the pyrin is represented with four domains and two motifs. Mutations p.M680I, p.M694V, p.M694I, p.K695R, p.V726A, and p.A744S, which are located in the B30.2 domain of pyrin protein, are responsible for manifestation of the most common and severe forms of FMF. All the domains and the motifs of pyrin, are directly or indirectly, involved in the protein–protein interaction with proteins of apoptosis and regulate the cascade of inflammatory reactions, which is impaired due to pyrin mutations. It is well known, that malfunction of the pyrin‐caspase‐1 complex is the main reason of inflammation during FMF. Complete tertiary structure of pyrin and the effects of mutations in it are experimentally not studied yet. The aim of this study was to identify possible effects of the abovementioned mutations in the B30.2 domain tertiary structure and to determine their potential consequences in formation of the B30.2‐caspase‐1 complex. Using in silico methods, it was found, that these mutations led to structural rearrangements in B30.2 domain tertiary structure, causing shifts of binding sites and altering the interaction energy between B30.2 and caspase‐1.