In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently large fraction of the population (e.g. 1% or more), many publications do not apply such a frequency threshold.

For example, at a specific base position in the human genome, the G nucleotide may appear in most individuals, but in a minority of individuals, the position is occupied by an A. This means that there is a SNP at this specific position, and the two possible nucleotide variations – G or A – are said to be the alleles for this specific position.

SNPs pinpoint differences in our susceptibility to a wide range of diseases (e.g. sickle-cell anemia, β-thalassemia and cystic fibrosis). The severity of illness and the way the body responds to treatments are also manifestations of genetic variations caused by SNPs. For example, a single-base mutation in the APOE (apolipoprotein E) gene is associated with a lower risk for Alzheimer's disease.

A single-nucleotide variant (SNV) is a variation in a single nucleotide. SNVs differ from SNPs in that a SNV can be somatic and can be caused by cancer, but a SNP has to segregate in a species' population of organisms. SNVs also commonly arise in molecular diagnostics such as designing PCR primers to detect viruses, in which the viral RNA or DNA sample may contain SNVs.