A specific difference in DNA sequence among individuals that can influence traits or disease susceptibility.A genetic variant is a place in the DNA where one person's sequence differs from another's, or from a reference sequence. The most common kind is a single-letter change, called a single nucleotide polymorphism, but variants also include small insertions or deletions, repeated stretches of sequence whose length varies, and larger rearrangements. Variants are the raw material of biological difference: they underlie traits such as eye colour and height, influence the risk of many diseases, and determine how a person responds to certain drugs. Most variants have no noticeable effect at all — they simply mark regions of the genome that differ between individuals. A variant becomes medically or biologically interesting when it changes how a gene works, for instance by altering a protein's building instructions or by switching a gene on or off in the wrong tissue or at the wrong time.
The idea that inherited differences come from discrete changes in hereditary material dates to early twentieth-century genetics. The modern study of variants at the level of individual DNA letters took off in the 1970s with methods for reading short stretches of sequence, and expanded enormously with the sequencing of the human genome, completed in draft form in 2001.
DNA is copied by molecular machinery that occasionally inserts the wrong letter or slips on repeated sequences, and these copying errors are the source of new variants. Environmental damage, such as ultraviolet light or certain chemicals, adds to the tally. Once a variant appears in a sperm or egg cell, it can be passed to the next generation, where natural selection and random chance determine whether it becomes common or disappears. Whether a variant produces a visible effect depends on where it sits: a change inside a gene's coding region may alter a protein, while a change in a regulatory region may affect how much of that protein is made.
Variant testing is used in clinical genetics to diagnose inherited disorders, in cancer care to match tumours to targeted drugs, and in large population studies that link variants to disease risk.
Any two unrelated humans share roughly 99.9 percent of their DNA sequence, so the differences that make each person distinct come from a small fraction of the genome.