Bardet-Biedl syndrome is a heterogeneous, multisystem disorder of ciliary function with variable expressivity within families. One model for in-complete penetrance invokes recessive inheritance with a heterozygous modifier at a second locus. Leen Abu-Safieh and colleagues now provide direct evidence against this model by using the most direct experimental approach (Eur. J. Hum. Genet. 20, 420–427, 2012). They sequenced the entire coding and flanking intronic regions of BBS1 to BBS14 in all affected individuals and their unaffected relatives from 29 families with Bardet-Biedl syndrome, finding only a homozygous mutation in a single gene in each affected individual and no evidence for third alleles. Homozygous mutations were not found in unaffected individuals. The study families were, with just one exception, consanguineous, but the allelic and locus heterogeneity found argues that the results are likely to apply to other populations. The authors note that their 100% rate of mutation detection is much higher than that of foregoing studies. Cryptic splicing mutations can be missed by DNA sequencing approaches, and their presence in compound heterozygotes can lead to the erroneous conclusion of triallelic inheritance.