An Arg457Gln variant in the CREBRF gene (encoding for Cyclic AMP Response Element Binding Protein 3 Regulatory Factor) has recently been identified as an important driver of excess body weight in numerous Pacific/Oceanic populations. Intriguingly, despite the substantial increase in body mass, carriers of the Arg457Gln variant had a paradoxical reduction in their risk for type 2 diabetes, indicating that this gene has a critical role in whole-body metabolism. To study the function of this variant in more detail, we have generated mice on an FVB background where this CREBRF Arg457Gln variant has been knocked in to replace the endogenous CREBRF. The whole-body metabolic phenotype was characterised for male and female mice on a regular chow diet or a high-fat challenge for 8 weeks. Regular assessment of body composition found no genotype effect in either sex: total body weight was not significantly altered at any time-point; measurement of fat mass by EchoMRI similarly showed no influence of the CREBRF variant on total adiposity. No differences were observed in the weights of individual adipose depots. Glucose and insulin tolerance tests demonstrated diet-induced defects in glucose homeostasis and insulin action, with no obvious effect of the CREBRF variant. Fasting blood glucose levels were likewise impacted by diet, but unaffected by genotype. Overall, this novel mouse model appears to show no significant effect of the CREBRF variant on any metabolic characteristics studied, with any visible differentiation due only to sex and/or diet effects. This inability to recapitulate the results of human association studies may invite reconsideration of the precise mechanistic link between CREBRF function and the risk of obesity and diabetes in variant allele carriers.