Genetic Variant

Key facts

Current human reference

GRCh38 (older data often uses GRCh37)

Naming standard

HGVS nomenclature

Short variant catalog

NCBI dbSNP, which assigns rs identifiers

Clinical assertions archive

NCBI ClinVar

What is a genetic variant?

Every person carries millions of differences from the human reference genome. Each difference is a variant. Most have no known effect on health, some are common in the population, and a small number cause or raise the risk of disease or change how a person responds to a drug.

Genetics professionals now prefer the neutral word variant over mutation and polymorphism. Mutation implied harm, and polymorphism implied a common variant, so both terms caused confusion in clinical reports.

Types of genetic variants

Variants are usually grouped by size and structure:

• Single nucleotide variant (SNV): one base replaced by another.
• Insertion or deletion (indel): a small number of bases added or removed; in a coding region this can shift the reading frame.
• Copy number variant (CNV): a larger segment deleted or duplicated.
• Structural variant: inversions, translocations and other rearrangements.
• Repeat expansion: a short repeated sequence that grows beyond its usual length.

Why genetic variants matter

Variants are the unit of analysis for genetic testing, companion diagnostics and pharmacogenomics. Drug labels, trial eligibility criteria and coverage policies often name specific variants, so knowing how many patients carry a variant is a direct input to market sizing and trial feasibility.

Joining variant data across sources is harder than it looks. The same variant can be written in genomic, transcript or protein terms, on GRCh37 or GRCh38 coordinates, and against different transcripts. Normalizing to HGVS descriptions or to database identifiers such as dbSNP rs numbers and ClinVar variation IDs is the first step before counting or matching.

Common misconceptions about variants

A variant found in a gene linked to a disease is not automatically disease-causing. Its clinical meaning depends on a formal variant classification, and many variants are reported as a variant of uncertain significance (VUS) until more evidence exists.