Background: The 1061delC single-nucleotide polymorphism (SNP) has been reported mostly in the context of the common A2 [A201] allele and typically produces an A2 phenotype. This study evaluated new A weak alleles, each containing 1061delC. STUDY DESIGN AND Methods: Twenty samples were referred to our laboratory for analysis due to suspected Aweak phenotypes originally detected at the referring centers. ABO Exons 1 through 7 and flanking intronic regions were sequenced. A antigen expression on red blood cells was analyzed by flow cytometry. Plasma enzyme activity was studied in one case. Molecular three-dimensional modeling techniques studied the potential effects of amino acid changes on the resulting glycosyltransferases (GTs). Results: Thirteen alleles were discovered, each featuring 1061delC with at least 1 of 12 additional SNPs in the coding region. One of these SNPs disrupts the translation initiation codon. Another constitutes the first reported change in the DVD motif. One SNP found in three alleles causes a substitution of one of the four amino acids that differentiates the wild-type A and B enzymes but plasma enzyme analysis by two methods showed only slightly decreased or normal A2 activity. Flow cytometric analysis semiquantified the A antigen levels in 16 cases featuring 10 of the alleles and ranged from very weak to nearly A2 levels. However, the majority of the samples displayed Ax-like patterns. Molecular modeling of some of the GT variants indicated conformational changes that may explain the diminished A expression observed. Conclusion: Missense SNPs were identified in 13 novel A2 -like alleles, which produced a variety of A subgroup phenotypes.