NM_017763.5:c.1403C>T (p.Ser468Leu) is a missense variant in RNF43 absent from gnomAD v2.1 and v4.1 population databases (PM2_Supporting).¹ No additional pathogenic or benign criteria are met. The variant is absent from ClinVar, has not been reported in the literature, and in silico predictions are equivocal (REVEL 0.37, BayesDel -0.227, SpliceAI max delta 0.01).² Based on generic ACMG/AMP 2015 classification rules, PM2_Supporting alone is insufficient to classify this variant as Likely Pathogenic or Likely Benign. The variant is classified as a Variant of Uncertain Significance (VUS).³