For the first time, our results confirm other worldwide studies for other populations for the positive association of the PNPLA3 rs738409 C>G variant with the presence of MASLD with liver fibrosis, the severity of hepatic steatosis and liver fibrosis in MASLD, and increased alanine aminotransferase levels among Egyptian subjects. This evidence concerns the gene PNPLA3 and metabolic dysfunction-associated steatotic liver disease.