NM_002529.3:c.1334G>A (p.Arg445Lys) is a missense variant in exon 11 of NTRK1. This variant is absent from all population databases: gnomAD v2.1, v4.1, and gnomAD-Canada (allele frequency 0.0; PM2 met at moderate strength).¹ Multiple lines of computational evidence predict a benign effect: REVEL 0.277, BayesDel -0.176, SpliceAI max delta 0.00 (BP4 met at supporting benign strength).² No published literature, ClinVar submissions, or functional studies specific to this variant were identified.³ NTRK1 loss-of-function variants cause autosomal recessive congenital insensitivity to pain with anhidrosis (CIPA); missense variants are a known disease mechanism. Applying generic ACMG/AMP 2015 final classification rules (PMID:25741868): one moderate pathogenic criterion (PM2) and one supporting benign criterion (BP4) are insufficient to classify as likely pathogenic or likely benign. The variant is classified as a Variant of Uncertain Significance (VUS).⁴