We have shown that SDHAF3 interacts directly with SDHB (residue 242 being key to this interaction), and that a variant in SDHAF3 (c.157 T > C [p.Phe53Leu]) appears to be more prevalent in individuals with pheochromocytomas and/or paragangliomas, and is hypomorphic via impaired interaction with SDHB. This evidence concerns the gene SDHAF3 and hereditary pheochromocytoma-paraganglioma.