 Finotype-phenotype correlations in CF may be complicated by variations of phenotypes and existence of complex alleles. We aim to elicited the clinical significance of complex alleles containing different mutations and for this we use the collaborative study of 153 patients from different CF French centers and structure function analysis for the single mutations are complex alleles mutations. Only three subjects have clinical CF and all carried the mutation P0G149R and this mutations is always present in complex alleles with two other mutations in CIS. Genotypes combining other mutants that do not contain this mutation were observed in patients with moderate phenotypes as CFTRRG and mostly CBIVG. Functional studies performed on all single and natural complex mutants showed that firstly this mutation P0G149R results in a severe mis-processing defect. Secondly, this mutation moderately alters CFTR maturation and thirdly the two other mutations often associated in CIS mildly alters CFTR chloride conductance. Overall, the results consistently show the contribution of this mutation P0G149R to the CF phenotype and suggests that the other mutations and other complex alleles are associated with CFTRRG, the presence study and phases in the importance of comprehensive genotype phenotype and functional studies in eliciting the impact of mutations on clinical phenotype. If you are happy and if you have questions about this paper you can join me at this address.