I've been struggling with this for a while and just a lot of failed, over exposed timelapses to show for it.

Scenario is taking a standard sunset timelapse using qDslr with holy grail and auto NTC.

At some point the exposure changes due to an unexpected event, maybe clouds appear and reflect the sun, a street light or something else. Sometimes even the scene just lightens and needs toning down not to burn out.

That needs a manual intervention to bring the exposure down and leads into my problem.

If i just for example alter the camera settings to bring the exposure down a stop the setup ends up dialling the settings back up over a few intervals.
If i try to do it by clicking on and reducing the reference value it seems to have no effect at all, even after a minute or two and 10+ clicks (by which time the timelapse is ruined anyway).

So my basic question is:- How do you make a manual, sudden change in the exposure during a timelapse *and* get it to stick as the new default brightness from that point forward?

Usually from my experience there are rarely such quick changes in reality (or the timelapse would be ruined anyway).
Changing the reference is usually the way to go. But it's a slower process, because you only change the reference indirectly and it will take time for the exposure to adjust. In 99.99% of all cases this works perfectly.

However, if you really have a scenario like yours, your best option would be to turn off Auto Holy grail, change the Exposure/ISO, wait for the next capture and then turn it on again.

Ive not had much luck changing reference even with 10-20 clicks and a few minutes nothing much seems to happen exposure wise.

Not tried turning HG off to make an adjustment then putting it back on though - would it not try to restore the previous reference it had set or will it reset to whatever it is when re-enabled?

You need to understand what the reference is and how it works. Then you will see that it can only change slowly and only in one direction (usually). It's not suited for quick changes. I've explained that in detail in this tutorial: https://lrtimelapse.com/gear/dslrdashboard/
If you turn off Auto HG, then change your settings and after you got a preview with the new settings turn on Auto HG again, you'll get a different reference value and from there on, the algorithm will try to preserve that brightness.

I was aware of how much reference changed which is why i was looking for a more rapid method to intervene before things start going wrong.

Toggling off auto HG then reenabling it after changes sounds like exactly what i was looking for though so i'll give that a go.

Similar issue on this timelapse, basically cityscape day to night with a bridge in foreground. About 20 mins after sunset bridge lights come on (so over exposes badly and as it ramps, continues to do so).

Is the best option there to just stop all holy grail and ramping and just manually adjust?

Once the highlights in Cityscapes start clipping you need to turn off the ramping at all. There should not be any ramping happening now anymore (neither auto nor manual) because those lightest parts will stay a their brightness no matter what. Just leave the camera running with fixed exposure when you notice that the artificial lights start clipping.