The worldwide outbreak of the highly pathogenic avian influenza (HPAI) H5N1 virus has sent egg prices soaring. Concomitantly, bovine and human infections of H5N1 viruses have also been observed, but there is no known person-to-person spread. The shape of the motifs is important for receptor recognition of viruses and is contradictorily deformed with amino acid mutations to avoid immunity. The deep neural network-based conformational variability prediction system of protein structures (SSSCPreds) suggests that the outbreak of HPAI is occurring in the avian world, just as the outbreak of SARS-CoV-2 was seen in the human world. The predicted flexible motif with the mutations N236K/Q238L of the B3.13 virus rationally explained the difference of specificity switching by the mutations between B3.13 and wild-type viruses, and the B-factor values were consistent with the prediction by SSSCPreds. Although the difference of only three common amino acid mutations T211I, V226A, and R341K near the sialic acid-dependent pathway and the furin cleavage sites exists between B3.13 and D1.1 viruses, the mutations of Q338L/R341K, which show the predicted rigid map pattern of the C-terminus, are one of the remarkable factors for the large difference of the case numbers for the bovine and human infections between B3.13 and D1.1 viruses.