The c.443G>A (p.Trp148Ter) variant in GP1BB is a nonsense variant that may cause loss of function of the protein, however, it is predicted to escape nonsense mediated decay and remove 28% of the protein (PVS1_Strong). This variant has been detected in at least 2 unrelated probands with Bernard-Soulier syndrome. One proband was homozygous for the variant (0.5 points, PMID: 12447957). The second proband was compound heterozygous for this variant and a pathogenic or likely pathogenic variant that was confirmed in trans by parental testing (22q11.2 deletion including GP1BB, 1 point, PMID: 23566026, PM3). At least one patient (Patient 1 in PMID: 23566026) with this variant had less than 10% expression of GPIba and GP9 compared to controls. The patient also had excessive mucocutaneous bleeding and macrothrombocytopenia which are consistent with Bernard-Soulier syndrome. Full gene sequencing of GP1BA, GP1BB, and GP9 were performed as well as del/dup analysis (PP4_Moderate). The Grpmax filtering allele frequency in gnomaDThe Grpmax filtering allele frequency in gnomaDv4.1 is 7.700e-7 (based on 3/1034782 alleles) in the European (non-Finnish) population, which is below the <0.0000651678 threshold for PM2_supporting. Surface expression of GP1BB and GP9 measured by flow cytometry and Western blot in HEK293T cells transiently co-transfected with the NM_000407.5:c.443G>A variant GP1BB and wild type GP1BA/GP9 showed decreased expression at 0% WT levels, indicating that this variant impacts protein function (PMID: 12447957)(PS3_supporting). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal recessive Bernard-Soulier syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PVS1_Strong, PP4_Moderate, PM3, PM2_Supporting and PS3_Supporting (VCEP specifications version PILOT).