en Bioinformatic Bioinformatic Original Article Original Article <div style="text-align: justify;">Genetic variations found in the coding and non-coding regions of a gene are known to influence the structure as well as the function of proteins. Serine palmitoyltransferase long chain subunit 1 a member of &alpha;-oxoamine synthase family is encoded by <em>SPTLC1</em> gene which is a subunit of enzyme serine palmitoyltransferase (SPT). Mutations in <em>SPTLC1</em> have been associated with hereditary sensory and autonomic neuropathy type I (HSAN-I). The exact mechanism through which these mutations elicit protein phenotype changes in terms of structure, stability, and interaction with other molecules is unknown. Thus, we aimed to perform a comprehensive computational analysis of single nucleotide polymorphisms (SNPs) of <em>SPTLC1</em> to prioritize a list of potential deleterious SNPs and to investigate the protein phenotype change due to functional polymorphisms. In this study, a diverse set of <em>SPTLC1</em> SNPs were collected and scrutinized to categorize the potential deleterious variants. <a name="_Hlk614461">Our study concordantly identified 21 non-synonymous SNPs as pathogenic and deleterious that might induce alterations in protein structure</a>, flexibility and stability. Moreover, evaluation of frameshift, 3&rsquo; and 5&rsquo; UTR variants shows c.*1302T>G as effective. This comprehensive <em>in silico</em> analysis of systematically characterized list of potential deleterious variants could open avenues as primary filter to substantiate plausible pathogenic structural and functional impact of variants.</div> single nucleotide polymorphisms, computational, deleterious, variants, bioinformatics tools 67 83 http://ijmcmed.org/browse.php?a_code=A-10-1604-1&slc_lang=en&sid=1 Tayyaba Sadaf taibsadaf@gmail.com 100319475328460016005 100319475328460016005 No Department of Health Care Biotechnology, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, Pakistan. Peter John pjohn@asab.nust.edu.pk 100319475328460016006 100319475328460016006 Yes Department of Health Care Biotechnology, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, Pakistan. Attya Bhatti attyabhatti@gmail.com 100319475328460016007 100319475328460016007 No Department of Health Care Biotechnology, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, Pakistan.