Focusrite 18i20 - guitar direct clipping

I think your Focusrite might use the same pre amps and mix control my 6i6 uses. 
First, If this is an electric guitar you really are better off using a DI. 
I find the pre amps are not very good at electric guitar or bass so I use other options for those. And yes they will clip because they are overly sensitive IMHO. 
So if you have a DI use that and the XLR input. 
Electric guitars give the best tone when they are connected to a guitar amp or guitar pre amp. You'll get a thin sound when using the instrument input. 
The instrument input works fine with acoustic electrics and active basses which both have pre amps. 
 
Your reference to a cable is instrument cables are Tip/Sleeve or TS and are not balanced. This is the correct cable for a guitar or bass and most keyboards. Balanced cables are Tip/ring/sleeve  TRS and are used for longer cable runs between balanced equipment, like a mixer or powered speakers. TRS and XLR are more or less the same balanced cable, just different connections.
 
Your DI box will convert your hi impedance guitar output into a Low Impedance balanced signal. But depending on the DI you will always be better off either miking a amp, or sometimes the using the amps line out or a good quality guitar pre amp like a Sans Amp. 
Radial DI's are the exception. 
 
I have used the Combi jack set to instrument in Mix Control for bass and guitar in a pinch, but you have to play very smooth and evenly, or put at least a compressor pedal ahead of it. I'm not a fan of the Focusrite pre amps for this very reason. I do not have this issue when using my Tascam. 
 

Thanks for the help guys - much appreciated. I have a cheap Rolls Matchbox DB25 DI box I will try. And I didn't evn think about changing anything in the Mix Control. See - over a year now with SPLAT as my first DAW and I am still learning things and making rookie mistakes.

Cactus Music
 The Rolls DI is not really of the caliber to make any difference.  

I did not think it would be - I have not even tried using it. I bought it years ago and used it for bass guitar for live performances.

I have also found that when working with a DAW, it is best to leave Mix Control open, even if minimized. I have noticed weird behavior if it is not actually open, so popping it open after the interface is turned on seems to keep things in order.
 
At first I actually though you had to have it running but since found unless you need to make a change this is not so. So myself I only open it to toggle the PAD/Line switches. I leave my buffer at 7ms which seems to cover all modes of what I do. 
At first I learned all the monitoring settings and found it pretty cool, but I did not like having to keep the screen open on my second monitor while I worked. So now I use a small mixer for headphone balance.