Leigh syndrome is a mitochondrial condition that causes severe neurological damage begin-ning early in life. By determining the possible harmful consequences of missense single nucle-otide polymorphisms in the SURF1 and NDUFV1 genes linked to Leigh syndrome, this work seeks to clarify the molecular process of the illness. In the study, deleterious single nucleotide polymorphisms were identified using bioinformatics tools such as SIFT, PolyPhen-2, Predict-Protein, PHD-SNP, SNP&GO, PANTHER and Meta-SNP, then their changes on protein in-tegrity were analyzed using I-Mutant 2.0 and MUpro. The findings indicate that certain single nucleotide polymorphisms may significantly disrupt protein structure and stability, increasing the risk of Leigh syndrome. Using STRING and GeneMANIA databases, the interaction net-works of these proteins with other proteins were examined, providing a more comprehensive understanding of the biological basis of Leigh syndrome. In our study, 6 single nucleotide polymorphisms in the SURF1 gene and 11 single nucleotide polymorphisms in the NDUFV1 gene were identified as potentially deleterious. Our study extends the previous literature on the genetic basis of Leigh syndrome and provides new information on the role of SURF1 and NDUFV1 gene mutations in disease pathogenesis. These findings may contribute to the cre-ation of diagnostic and treatment strategies for Leigh syndrome in the future.