NM_001123385.1:c.1005dupC (p.Ser336LeufsTer45) is a frameshift duplication in BCOR exon 4 predicted to undergo nonsense-mediated decay, meeting PVS1 at very strong strength under the ClinGen SVI PVS1 framework (PMC6185798). BCOR loss-of-function is an established germline disease mechanism associated with oculofaciocardiodental (OFCD) syndrome and hereditary hematopoietic malignancy predisposition.¹ The variant is absent from all large population databases including gnomAD v2.1, v4.1, and gnomAD-Canada, meeting PM2 at supporting strength.² The variant is absent from ClinVar with no submissions from clinical laboratories. It has been observed in somatic cancers (COSMIC, n=6) consistent with a tumor suppressor role, but no germline proband observations are currently documented in the literature or databases.³ Five publications (PMID:22012066, 22237022, 24047651, 25550361, 26847029) were reviewed and found to discuss BCOR mutations in somatic myeloid malignancies and retinoblastoma but none specifically mention NM_001123385.1:c.1005dupC. No variant-specific functional, segregation, or case-level evidence was identified for this variant. Applying generic ACMG/AMP 2015 final classification combination rules: PVS1 (very strong) + PM2 (supporting) supports a classification of Likely Pathogenic.⁴