Highly pathogenic avian influenza A(H5N1) viruses are expanding their host range among mammals, raising concerns about their pandemic potential. Building on recently published deep mutational scanning data1, we show that hemagglutinin retains structural plasticity to increase acid stability through independent mechanisms, including modulation of electrostatic interactions, hydrogen-bonding networks and hydrophobic packing that may facilitate human adaptation. These findings illustrate how structural analyses can strengthen genomic surveillance for pandemic risk assessment.