Introduction: Noonan syndrome is a genetic disorder (autosomal dominant) characterized by short stature, congenital heart disease, bleeding problems, developmental delays, and skeletal malformation. It is mainly caused by a single nucleotide alteration in four genes PTPN11, SOS1, RAF1, and KRAS . In this study, we computationally analyzed the SOS1 gene to identify the pathogenic non-synonymous single nucleotide polymorphisms (nsSNPs), which is known to cause Noonan syndrome. Hypothesis: We hypothesize that in-silico analysis of human SOS1 mutations in Noonan syndrome would be a promising predictor to study the post-translational modifications. Methods and Results: The variant information of SOS1 was collected from the dbSNP database and the literature review on Noonan syndrome. They were further analyzed by in-silico tools such as I-Mutant, iPTREE-STAB, and MutPred for their structural and functional properties. We found that 11 nsSNPs are more pathogenic for Noonan syndrome. The 3D comparative protein of 11 nsSNPs with its wild-type SOS1 was modeled by using I-Tasser and validated via ERRAT and RAMPAGE. The protein-protein interactions of SOS1, GATA4, TNNT2, and ACTN2 were analyzed using STRING, which showed that HRAS was intermediate between SOS1 and ACTN2 (Fig. 1) . Conclusion: This is the first in-silico study of the SOS1 variant with Noonan syndrome. We proposed that this 11 nsSNPs are the most pathogenic variant of SOS1 , which helps to screen the Noonan patient. Furthermore, our results are promising to study the gain/loss of post-translational modification (PTM) by mutation in cardiac genes and helps to explore the novel molecular pathways.$graphic_{DB5B0E7D-4DA6-4569-A16F-E05B2C9C4D2F}$$