Usually harmful mutations are those which disrupt a vital function, what you might call "passively" harmful. What about a mutation that makes a protein, which is not just useless, but actually toxic to its host? Are there any known examples?
There are definitely examples! For one, you might consider sickle-cell anemia to fall into this category.
The mutation that causes this disease leads to abnormal strands of hemoglobin that distort the shape of red blood cells, to the point that those cells can directly disrupt blood flow.
Interestingly, carriers of the sickle-cell trait actually have some protection against malaria, which explains the high incidence of the allele despite the dangerous consequences of the disease.
You can find many other examples in the category of autosomal dominant disorders (though note that sickle-cell is considered recessive, though carriers can still have some negative effects). Because these disorders only require one copy of a gene to cause illness, there is often some toxicity of the mutated protein, whereas in what you refer to as "passively" harmful mutations, one healthy copy can often compensate, fully or partially. Of course these are general statements and there will always be exceptions, but I hope thinking about it this way can guide your curiousity!