Recent advances in paleo-genetics allowed the identification of protein-coding changes apparently fixed on the lineage leading to Homo sapiens, by comparing genomes of present-day humans and archaic hominins. Although such genomic differences are thought to make key contributions to distinctly modern human traits, experimental validation of their potential impact was so far restricted to functional assays and model organisms. With the availability of large-scale genetically informative population databases, it now becomes possible to identify present-day carriers of rare archaic alleles of interest and to directly assess putative phenotypic consequences in living humans. We queried exome sequencing data of around half a million people in the UK Biobank in search of carriers of archaic alleles at 37 genomic positions with supposedly fixed human-specific changes. This search yielded 103 carriers of the archaic allele for 17 positions, with diverging allele counts across ancestries. We contrasted carriers of an exemplary archaic allele in SSH2 with a curated set of non-carriers, observing no deviation from the norm in a range of health, psychological, and cognitive traits. We also identified 62 carriers of the archaic allele of a missense change in the TKTL1 gene, previously reported to have large effects on cortical neurogenesis based on functional analyses in brain organoids and animal models. However, human carriers of the archaic TKTL1 allele did not show differences in anatomical brain measures and qualification level, compared to non-carriers. These results highlight the importance of investigating diverse ancestral populations for a more accurate representation of shared human variation and challenge the notion of permanently fixed genetic changes that set Homo sapiens apart from Neandertals and Denisovans. Lastly, we propose that future investigations should assess effects of multiple archaic alleles in aggregate, since any single genetic change is unlikely to itself explain the emergence of complex human traits.Competing Interest StatementThe authors have declared no competing interest.