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Structural modelling confirmed that the missense variants may affect quaternary structures, causing protein instability. Our findings expanded the ACADS and ACADVL mutational spectra. The combination of in silico prediction and structural modelling can improve our understanding of the pathogenicity of unreported genetic variants, providing an explanation for variant assessment. Our findings expanded the ACADS and ACADVL mutational spectra. The combination of in silico prediction and structural modelling can improve our understanding of