NM_001274.5:c.157A>G (p.Lys53Glu) in CHEK1 is a missense variant absent from all gnomAD population databases (v2.1, v4.1, Canada), meeting PM2 at supporting strength.¹ No pathogenic or likely pathogenic variant has been reported at the same amino acid residue (Lys53) in ClinVar; PS1 and PM5 are not applicable.² Multiple lines of in silico evidence do not support a deleterious effect: REVEL 0.271, BayesDel -0.154, SpliceAI max delta 0.00. PP3 is not met.³ PVS1 is not applicable as this is a missense variant not falling into null-variant buckets defined by ClinGen SVI PVS1 recommendations (PMC6185798).⁴ No functional studies (PS3/BS3), segregation data (PP1/BS4), de novo observations (PS2/PM6), case-control data (PS4), phenotype data (PP4), or ClinVar classifications (PS5/PP5/BP6) are available for this variant.⁵ With PM2_supporting as the sole met criterion, the variant is classified as a Variant of Uncertain Significance (VUS) under ACMG/AMP 2015 rules.⁶