Grand unification theories, such as $SU(5)$/$SO(10)$/SUSY variants, suggest proton decay. The lack of observational evidence for proton decay rules out simple GUTs.
But wait a minute! The GUT's prediction of proton half-life is based on the assumption that proton decays into positron (along with a neutral pion). According to Cosmas Zachos's comment on another PSE post, there is NO established generational linkage between up/down quarks (making up the proton) and electron/position. We might as well assume up/down quarks and muon/antimuon are in the same generation (as suggested here, whereas electrons and, say, top/bottom quarks are in the same generation). Hence proton should decay into antimuon, rather than positron (assuming GUT vertices involving X bosons are generation preserving).
If this is the case, the proton half-life is much longer than envisioned before, since muons are heavier than electrons. Therefore, the lack of observational evidence for proton decay does NOT disprove simple GUTs at all.