Yes, it makes a big difference. Here's why: With any propellent, the most uniform burn comes from a charge where the individual granules of powder are packed together. If there are any gaps, the burn will get interrupted, slow down, then start again. The surface area exposed to the primer flash is important.
Example: lets say a cartridge has been loaded only half full of powder that is laying in the bottom of the case. When the primer ignites, it will "see" more powder surface area and will initially ignite at least 4 times the powder than it would in a 100% loaded case. The pressure will peak very quickly, possibly to a dangerously high level. Then the pressure will drop until the remainder of the powder gets ignited. This causes a second peak and possibly a third peak.
Now we shoot a second round (same load). Because of recoil or gun position, the powder isn't laying in the case the same as it was on the first round. The second charge will ignite and burn much different than the first, thus different pressure and velocity.
In a 100% charged round, the primer ignites only the powder directly in front of it. In turn, the burning powder ignites the powder in front of it and so on until all the powder has burned. This creates a gradually increasing, single, predictable pressure peak. Each round fired will create a near identical pressure peak. A chronograph will prove the uniform velocity and the target will prove the accuracy.
Usually any rifle cartridge with 75% occupied space in the case will create one predictable peak. The closer you get to 100%, the more predictable the burn will be. If your bullet is occupying space in the case body, that counts.