First off I don't think you have a good understanding of how AE handles files or how compression works. You should NEVER use compressed footage in your production pipeline. Every time you re-compress MPEG footage you add artifacts. Even decoding h.264 files can cause problems in some footage. This scan happen because there are more frames in h.264 video that are not really there. The in between frame are created by averaging the real frames, I'm mean frames with actual pixel by pixel color and luminance values for each pixel that are on either side of the frames the computer creates on the fly from the real frames in the file. That's how they get the small file sizes. They throw away at least 1/3 of the original data and let the computer guess what those frames should look like.
There is nothing wrong with using uncompressed video as a source in AE, in fact uncompressed or at least visually lossless is by far the preferred format for all footage you use in a production. H.264 is only a delivery format and it should be the very last step in the production process.
Second point, if you are rendering h.264 from AE's render cue and output module you are using a very poor and not recommended workflow. The output module's primary use is to render visually lossless footage for further use in the production process. If you want to render for delivery you should be using AE's media encoder. If you want to use Handbrake to render the deliverable product then you should NEVER be supplying handbrake with MPEG files unless there is no other alternative.
Last point, what format is your original footage. You say uncompressed but that doesn't really tell us anything. If the footage is truly uncompressed or visually lossless then that is what you should be using as source material.
BTW, AE does not make any changes to the source files. AE is completely non destructive.
OK - makes sense. The files have been generated by an animation program using None (uncompressed 8-bit) as the selected output (MOV). When AE is finished compositing the credits overlay and doing the fades, I"ll do an output render also using None - will try the Media Encoder, but I assume it will produce similar output to the Render Que since it will be uncompressed like the original input files. Just hope that Handbrake can accept the result - probably >400 GB.
If all you were doing is a credit roll and some trades you will be much better off using Premier Pro and rendering directly to H.264 using the Adobe media encoder directly out of Premier. You should only be using After Efects to create "effects and composites" that you cannot do in a nonlinear editor. You can set up the bit rate and multipass or just use one of the standard presets and get a really good H.264 MP4 file. There is hardly anything to gain in almost any video file by using Handberak. And unless you are really a encoding and compression expert you shouldn't do much monkeying with the settings anyway.
I know there are some that would argue Handbrake does a better job but that has not been my experience. Any differences that there may be would be hard to spot without a comparison of the two rendered files using some fairly sophisticated frame checking workflow.
Did you ever solve this issue? Let us know what happened.