X-linked hypophosphatemia is the most common cause of inherited rickets, due to inactivating variants of PHEX. More than 800 variants have been described to date and one which consists of a single base change in the 3′ untranslated region (UTR) (c.*231A>G) is reported as prevalent in North America. Recently an exon 13–15 duplication has been found to occur in concert with the c.*231A>G variant, and thus it is unclear whether the pathogenicity is solely a function of the UTR variant. We present a family with XLH who harbors the exon 13–15 duplication but does not carry the 3′UTR variant, providing evidence that the duplication itself is the pathogenic variant when these two variants are found in cis.