NM_001274.5:c.1148A>T (p.Lys383Ile) is a missense variant in CHEK1. The variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada, meeting PM2 at supporting strength.¹ No pathogenic or likely pathogenic classifications exist in ClinVar. No functional studies, de novo reports, co-segregation data, or case-control evidence are available for this variant.² In silico predictors are discordant: REVEL 0.433 is intermediate, BayesDel -0.14524 is benign-leaning, and SpliceAI predicts no splicing impact (max delta 0.01). The computational evidence does not meet PP3 or BP4 thresholds.³ CHEK1 lacks ClinGen-curated gene-disease validity, and no CSPEC or VCEP framework is available. Criteria dependent on established disease association (PP2, PP4) could not be reliably assessed. Applying the generic ACMG/AMP 2015 combination rules (PMID:25741868), the single supporting pathogenic criterion (PM2) is insufficient to reach Likely Pathogenic, and no benign criteria are met. The variant is classified as a Variant of Uncertain Significance (VUS).⁴