Introduction: This is the first patient with CVID with a new heterozygous variant in NFKB1 followed by Autoimmunity and Immunology Department from Hospital El Cruce. Clinical Case: She is a 40 years old patient with a history of cytopenias and chronic lymphoproliferation. She was referred from the Hematology Unit because of the presence of cytopenias with unknown etiology. Familial Background: Mother died at 28 years old because of SLE and she has a young daughter suffering from cytopenias. She reports seizures during infancy, an isolated episode of pneumonia when she was 20 years old, pharyngitis, and oral thrush associated with leukopenia. In 2018 she was admitted for the first time due to leukopenia and thrombocytopenia, bone marrow punction was normal and a PAN-CT revealed multiple cervical and iliac adenopathies with a homogeneous hepatosplenomegaly. Lymph node biopsy showed reactive follicular hyperplasia and liver biopsy presented CD8+T Cells lymphoid infiltration, without plasma cells. Complete autoantibodies panel was negative. Because of the presence of cytopenias and chronic lymphoproliferation, ALPS was suspected. Initial lab tests showed high levels of B12 vitamin and DNTcell of 4.5% associated with hypogammaglobulinemia. She started with steroids, with a good initial response. Unfortunately, she was admitted several times due to severe cytopenias and lymphoproliferation. An extended molecular panel revealed a pathogenic five nucleotide insertion in the exon 11 of NFKB1 (p.Val313Fs – c.936_937insTTGG) in heterozygosis, not reported yet. This insertion produces a subsequent frameshift in a conserved region. With these results, CVID with an ALPS-like phenotype was assumed. She is under treatment with a low dose of steroids and waiting for health insurance to provide Immunoglobulin treatment. Her daughter was diagnosed with the same variant. Discussion: Autoimmune cytopenias and lymphoproliferation are common symptoms of IEI, despite no recurrent infections.