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Reasons from particulate inheritance, segregation, recombination, allele frequency, and genotype-phenotype evidence through ACMG/AMP-ClinGen classification, gnomAD/ClinVar/OMIM, HPO phenotyping, and PLINK/GATK/VEP QC while treating sample swaps, cryptic relatedness, population stratification, LD tagging, phenocopies, winner's curse, and build/transcript mismatch as first-class failure modes.