Guthrie scored from a free-kick in each half - the first, in a clearly unintended manner - to stretch Reading's unbeaten run in the Championship to five matches.
"The difference in the game for me was two top-class set-plays from which we've come undone," Clark said.
"With the first free-kick, sometimes you've got to hold your hand up and say it was the quality of the delivery that caused us the problems.
"When you fizz it in at that speed and there's players running across the goalkeeper's eyeline, it makes it difficult.
"We could still have taken something from the game if we'd had more composure and made the right decisions and had a bit more of a cutting edge in the final third.
"We made the wrong decisions at the wrong times. In terms of our general performance, I was pleased. We passed the ball around well and competed."
Birmingham appeared in fine fettle, with a 4-1 league win over Sheffield Wednesday prior to their 3-1 defeat of Swansea, the holders, in the Capital One Cup third round at St Andrew's in midweek.
But the home side were dominant from midway through the first half to the end, playing a patient brand of football that Birmingham had little answer to.
Guthrie made the breakthrough in the 32nd minute after Chris Burke had been penalised for handball.
He swung in the free-kick from wide out on the left and, to Randolph's horror, the ball somehow found its way through a crowded area and into the far corner of his net.
Reading, winning for a third successive match and having taken 13 points from a possible 15, secured the victory in the 75th minute.
Dan Burn fouled Robson-Kanu on the edge of the Birmingham area and Guthrie curled in the free-kick via Randolph's near post.