NM_002529.3:c.737C>T (p.Ser246Phe) is a missense variant in NTRK1, a gene associated with autosomal recessive congenital insensitivity to pain with anhidrosis (CIPA). This variant is absent from gnomAD v2.1 and present at extremely low frequency in gnomAD v4.1 (1/1,614,010 alleles; overall AF=6.20×10⁻⁷; highest subpopulation AF=1.10×10⁻⁵ in South Asian), satisfying PM2 at moderate strength.¹ Multiple in silico tools predict a benign effect: REVEL score of 0.132, BayesDel score of -0.415, and SpliceAI max delta of 0.01. These support BP4 at supporting benign strength.² This missense variant is not eligible for PVS1 as it does not fall into the null-variant buckets of nonsense, frameshift, or canonical splice site variants per ClinGen SVI PVS1 recommendations (PMC6185798).³ No functional studies, de novo reports, segregation data, case-control data, or ClinVar classifications exist for this variant. No publications mention NM_002529.3:c.737C>T. The evidence profile consists of PM2 (moderate) and BP4 (supporting benign). Under generic ACMG/AMP 2015 combination rules, this combination does not meet the threshold for pathogenic, likely pathogenic, benign, or likely benign classification, and the variant therefore remains a variant of uncertain significance (VUS).⁴