OBJECTIVE: To identify the PNPLA3 genetic variants as the potential predictors for metabolic associated fatty liver disease (MAFLD) and its progression among Pakistani population. METHOD: A cross sectional study comprising of 158 participants. They were included in this study with non-probability purposive sampling technique from Radiology Department of Aziz Fatimah Teaching Hospital and Aziz Fatimah Medical and Dental College, Pakistan. The duration of study was December 5, 2021 to April 4, 2024. Blood samples (10mL) were drawn for liver enzymes, gene analysis and ultimately PCR products were sent for Sanger sequencing. Data was analyzed using SPSS version 26 with p-Values ≤0.05 considered significant. RESULTS: From 158 studied participants, 43.7% were male, and 56.3% were female. Of total population 51.3% were MAFLD positive while 48.7% were control subjects. Present results showed that CT and TT genotypes of rs738408 were frequently found in MAFLD group (p=0.039 and 0.060, respectively) and significant predictor for developing MAFLD (OR=2.484, p=0.019 and OR=5.167, p<0.001, respectively). Concerning progression of the disease CT genotype showed that subject with this genotype progress to moderate grade of fatty liver disease (OR=2.832, p=0.013). Whereas Odd ratio for TT genotype was significant for severe grade fatty liver diseases (OR=15.50, p=0.007). GG genotype of rs738409 was frequently found in MAFLD group (p=0.032). Odds ratio for GG genotype of rs738409 was significant for developing MAFLD (OR=4.565, p=0.025) and responsible to progress to moderate grade of fatty liver disease (OR= 5.083, p=0.022). CONCLUSION: CT and TT genotypes of 738408 and GG genotype of 738409 are associated with MAFLD and are at more risk for disease progression.