Recent strides in computational structural biology have opened up an opportunity to understand previously mysterious uncharacterised proteins . The under-representation of transmembrane proteins in the Protein Data Bank highlights the need to apply new and advanced bioinformatics methods to shed light on their structure and function . This study focuses on such a family; transmembrane proteins containing the Pfam domain PF09335 (‘ SNARE_ASSOC ’ / ‘ VTT ‘ / ‘ Tvp38 ’). One prominent member, Tmem41b, has been shown to be involved in early stages of autophagosome formation and is vital in mouse embryonic development . Here we use evolutionary covariance-derived information not only to construct and validate ab initio models but also to make domain boundary predictions and infer local structural features . The results from the structural bioinformatics analysis of Tmem41b and its homologues show that they contain a tandem repeat that is clearly visible in evolutionary covariance data but much less so by sequence analysis . Furthermore, cross-referencing of other prediction data with the covariance analysis shows that the internal repeat features 2-fold rotational symmetry . Ab initio modelling of Tmem41b reinforces these structural predictions . Local structural features predicted to be present in Tmem41b are also present in Cl−/H+ antiporters . These results together strongly point to Tmem41b and its homologues as being transporters for an as-yet uncharacterised substrate and possibly using H+ antiporter activity as its mechanism for transport.