SERPINA1 and alpha 1-antitrypsin deficiency: The S variant (PI S, rs17580) and the Z variant (PI Z, rs28929474) are the major missense single-nucleotide polymorphisms (SNPs) leading to AATD by moderate and severe decline of AAT levels, respectively, through the conformational change of the AAT protein and the subsequent faulty secretion of AAT from hepatocytes12.