The X-linked recessive degenerative disease dystrophinopathy results from variants in the DMD gene. Given the large size and complexity of the DMD gene, molecular diagnosis for all dystrophinopathies remains challenging. Here we identified two cryptic exon retention variants caused by intronic single nucleotide variants in dystrophinopathy patients using combined RNA- and DNA-based methods. As one variant was previously unreported, we explored its likely pathogenic mechanism, via bioinformatic prediction for in silico verification of splicing. Then we constructed a minigene system harboring the variant and used morpholino modified antisense oligonucleotides (ASOs) to induce cryptic exon skipping. ASOs treatment corrected the mis-splicing in the mutant minigene system. Our study defines a novel intronic variant that can cause dystrophinopathy, and illustrates a strategy to overcome the aberrant splicing.