AbstractHuman monkeypox is a contagious zoonotic viral disease caused by Monkeypox virus and is causing a current outbreak in various regions of the world, being already considered an epidemic and a global public health problem. From the sequenced monkeypox genomes of clades B.1, A.1.1 and A.2 available, we performed analyzes of 9 proteins considered important in the pathogenesis of the disease (A9L, A36R, A50L, B9R, B16L, C3L, C7L, C12L (SPI-1) and H5R) and 4 important proteins for the host’s immune response (A27L, A33R, B5R and L1R). We identified four synonymous mutations and six amino acid changes, of which four are in conserved domains, such changes can alter the function of proteins. Furthermore, we did not find the C3L protein in monkeypox genomes from the 2022 outbreak, an important protein for disease pathogenicity. Our analyses suggest that lineage/clade A.2 may be suffering the different effects of various selective pressures than lineage/clade B.1. In conclusion, the mutations identified in the present study have not yet been associated with genetic alterations, significant changes in the transmission route, mean age, signs/symptoms at the clinical presentation, and their evolution could be detected. Therefore, further research in the field is needed since our findings need to be confirmed by new studies.