Introduction The addition of HLA-C to UNOS cPRA calculation was the result of increased recognition of the importance of HLA-C antibody and the fact that enough data was available on the frequency of HLA-C types in donors. The unacceptable cut-off for HLA-A/B/DR/DQ antibodies, which varies drastically throughout the HLA field, was determined based on the likelihood of producing a positive crossmatch. Will the same arbitrary cut-off apply to HLA-C? HLA-C has unique antigen expression level on the cell surface and limited antigenic polymorphism, which can create artificial over representation on Luminex Single antigen beads. This is an ongoing case study from one transplant center aiming to answer these questions. Methods Nine sera with HLA-C antibodies were identified; five of them only had HLA-C antibodies. The antibody profile and strength were characterized using Luminex single antigen bead assay (One Lambda Inc, Canoga Park, CA). Surrogate donor cells with corresponding DSA were collected and crossmatched using CDC, AHG-CDC and Flow methods. All HLA-C DSA(s) are >4000 MFI, which is the cut-off used in our center as unacceptable antigen determination and likely to produce positive CDC and/or AHG-CDC crossmatch. Results All CDC, AHG-CDC crossmatches were negative. Among the 4 sera with multiple loci DSA, 3 were T and B cell Flow positive and 1 was B cell positive only. Among the 5 HLA-C DSA only sera, 3 were T and B cell Flow positive and 2 were T and B cell Flow negative. Anti-Cw4 demonstrated positive flow T and B cell crossmatches with MFI’s over 4K range (5–8 K tested). Anti-Cw1, often observed as only HLA-C antibody sera together with Cw1/C15/C12, was completely negative for all T and B cell CDC, AHG-CDC and Flow crossmatches. Discussion If HLA-C unacceptable antigen cut-off is set at 4000 MFI, all of the above ‘donors’ would have been eliminated. At a center where transplants are routinely performed over positive DSA/Flow crossmatch, all of these cases would be transplantable, and furthermore, two of these cases would not require any immune modulation prior to transplant. An anti-Cw7 calculates as 49% cPRA and will cause a high percentage of donor exclusion. Is the Cw1/C15/C12 valid? Ongoing data collection is in progress for better defining HLA-C antibody and unacceptable cut-off for virtual donor exclusion.