NM_002529.3:c.1065C>A (p.Asn355Lys) is a missense variant in NTRK1, a gene in which loss-of-function variants cause autosomal recessive congenital insensitivity to pain with anhidrosis (CIPA).¹ This variant is absent from large population databases (gnomAD v2.1 and v4.1), supporting PM2 at moderate strength.² In silico predictors are inconclusive: REVEL score is 0.372 (intermediate, not reaching pathogenic thresholds) and BayesDel is -0.315 (benign-leaning). SpliceAI predicts no splicing impact (max delta = 0.00). PP3 and BP4 are not met.³ No functional studies, de novo reports, cosegregation data, or ClinVar submissions were identified for this variant. PVS1 does not apply as the variant is a missense substitution, not a null variant.⁴ Only PM2 (moderate) is met. Under generic ACMG/AMP 2015 combination rules (PMID:25741868), a single moderate criterion is insufficient to reach Likely Pathogenic or Likely Benign. The variant is classified as a Variant of Uncertain Significance (VUS).⁵