Background: The Clinical Genome Resource Consortium (ClinGen) recommends MaxEntScan (MES) model to predict the effects of LDLR splice variants. We developed “MaxSpliZer”, a software tool to automate the implementation of MES, and validated it using ClinVar and UK-Biobank (UKBB) data. Method: We tested concordance of MaxSpliZer predictions with ClinVar classifications of benign/likely benign (B/LB) and pathogenic/likely pathogenic (P/LP) for LDLR variants with potential effect on splicing. We also annotated LDLR splice variants in 200,618 UKBB participants, categorizing them using MaxSpliZer as deleterious (n=90) and non-deleterious (n=7,404). Low-density lipoprotein cholesterol (LDL-C) levels were compared in these two groups after adjustment for lipid-lowering medication use. Results: MaxSpliZer prediction was concordant with the ClinVar classification in 128 of 138 P/LP variants (sensitivity 93%) and 432 of 436 B/LB variants (specificity 99%). In the UKBB, splice variants predicted as deleterious by MaxSpliZer had higher LDL-C than non-deleterious splice variants (158.7±47.4 vs. 146.0±34.8mg/dL, p-value = 0.014). Compared to manual curation time of 12±7 min per variant, MaxSpliZer took 0.52±0.11 min for single entries and 1.5 s per variant for biobank-scale data. Conclusion: MaxSpliZer, a software tool that implements MES based on the ClinGen guideline, can accurately classify LDLR splice variants in a rapid automated fashion.