The CTNNB1 c.1149G>T (p.Trp383Cys) variant has been observed in somatic cancers 12 times in COSMIC and has also been reported in ClinVar, although ClinVar submission-level classification details were not available from the retrieved record.¹ This variant is absent from gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada, placing its observed population frequency at 0, below the 0.1% rarity threshold used for PM2.² In a published functional study of CTNNB1 armadillo repeat 5 and 6 substitutions, residue W383 was identified as recurrently mutated in cancer, and substitutions in this region were associated with reduced APC binding and increased downstream beta-catenin signaling, but direct functional testing of p.Trp383Cys was not established from the retrieved evidence.³ Computational findings are concerning for a missense effect, with REVEL 0.642 and BayesDel 0.287483, while SpliceAI predicts no meaningful splice effect with a maximum delta score of 0.02.⁴