Custom atmega2560 PCB w/ FT232R

I'm having some weird issues. I'm able to upload the bootloader through Arduino IDE or Atmel Studio 7, no issues. I just can't upload the sketch from Arduino IDE now. It times out. I have the driver installed for FT232, the loopback test does not work, and when I do try to upload, the TX light blinks randomly before it times out.

Any ideas?

I've attached the schematic.

do you have anything else hooked up to tx and rx pins while programming ? if it has please remove it then try

Hard to tell from the schematic, is the FT232R in any way connected to the RESET of the atmega2560? Usually it would be connected through a capacitor, otherwise you will have to manually reset the atmega2560 when uploading code.

Odd that the loopback test does not work, how are you connecting RX and TX during the test?