I entered my garage last night, and with key fob in pocket, tried to open the door. Lights flashing but would not let me in. Tried locking / unlocking with key fob, and still no change, could not get into the car. It took a good 2 mins before I remembered there is a physical key in the fob, so I used that to get in the car. Battery is good. Hasn't happened since.

Any ideas what could have caused this?

Radio interference. I've had this problem a few times.

Was it only the drivers door that didn't unlock, or all the doors?
If the lights flashed I would suspect that at least one door unlocked...depending how you have your unlock function set.

I have mine set to a single press, or touch of the handle, unlocks all doors, but the factory default is to unlock only the drivers door.
You can change this in the Navi menu.
If yours is still the factory default and the drivers door did not unlock, then the perception is you are locked out.
A quick double press of the Unlock button will open all doors at that point.

Having said all that, if the drivers door was the only one that didn't unlock, then i would suspect the actuator is likely starting to go. This has happened to a few owners.

Mine is set to unlock only the drivers door -- I've never changed any of the settings (don't have Nav in this vehicle, but maybe I could do that through the infotainment screen anyway?). Had this car almost 6 years and never really had a need to tweak settings, I liked the default.. and it has always worked fine for me, both in this one and the 2nd gen I had before it. But, in that incident, it did not unlock any of the doors, the double press or any of the normal tricks. It could be the actuator as you said, but it hasn't done it since. I'm not too worried about it because I've got a BMW 3 series on order (only a couple of more weeks)... just wanted something new. Weird that the f sport locked me out, it's kind of like she knows we will be breaking up soon and she's getting all hormonal about it

You can indeed change quite a few of the settings in the infotainment settings. You don’t have to have nav to do it. The lock settings is definitely one of many settings you can mess with in there.

this happens to me sometimes, go reach for the handle and it starts beeping and won’t open, the rear door opens though so I usually open the rear door and reach over and unlock the driver door manually and get it and forget it happens until the next time, I was wondering if changing the key fob battery would fix the issue but it doesn’t happen that often to remember to buy a new battery.

But has it ever done it where the rear doors stayed locked, and no amount of key fob presses or double presses could unlock it? The car lights/beep was responding to all key fob presses, it just said "nope" with regard to letting a human in the car.

It made me wonder if it was a protective response to a relay hack attempt (or just an snafu that the car confused for same)? The response from the car reminded me of other vehicles I've had, where the alarm system alerts you to something out of the ordinary the next time you unlock the car.

When is the last time you replace the key fob battery?

Both key fob batteries were replaced about 8 months ago -- and I tried both of them to rule that one out.

yes exactly the same but the rest of the doors open fine, change the settings to open all doors and maybe it will be the same. The fob won’t work and any try to open the door just keep beeping and flashing, pretty sure it’s interference of some kind.

I had that hapen to the drivers door. Luckily it was under warrenty as the dealer replaced the cable assembly and the actuator assembly.

glad to see i wasn't the only one having this issue

So far, it hasn't happened again.