NM_033632.3:c.1697G>T (p.Trp566Leu) is a missense variant in exon 11 of FBXW7, a gene in which germline loss-of-function variants cause a neurodevelopmental syndrome with Wilms tumor predisposition.¹ This variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada, meeting the PM2 criterion at supporting strength.² In silico prediction with REVEL yields a score of 0.863, supporting a deleterious effect and meeting PP3 at supporting strength.³ SpliceAI predicts no significant splicing impact (max delta score 0.12).⁴ This variant has been reported in somatic cancers (COSMIC COSV99662097, n=2) but has not been observed in ClinVar or any germline disease cohort.⁵ With only two supporting pathogenic criteria (PM2_Supporting, PP3_Supporting), this variant does not meet the threshold for Likely Pathogenic classification under generic ACMG/AMP 2015 combination rules.⁶ This variant is classified as a Variant of Uncertain Significance (VUS).⁷