Definitions of polymorphism and mutation

Definitions

Mutation and polymorphism both describe DNA sequence variation from a reference sequence - the terms are distinguished primarily by population frequency and clinical consequence, though modern genetics increasingly prefers the more neutral term "variant" for both, to avoid the value-laden connotations of "mutation" (harmful) vs "polymorphism" (benign)
Terminology conventions have shifted substantially in genetics practice over the past decade, with "variant" plus a standardised pathogenicity classification (pathogenic, likely pathogenic, VOUS, likely benign, benign) now preferred in clinical reporting over the older mutation/polymorphism dichotomy

Traditionally, a polymorphism was defined as a variant present in >1% of the population and generally without significant clinical consequence, while a mutation implied a rarer variant with a disease-causing effect - but this frequency-based distinction does not reliably track with actual clinical significance (some common variants do have disease associations, and some rare variants are benign)

Modern variant classification (ACMG/AMP framework) does not use "mutation" vs "polymorphism" as its primary categories - it classifies variants along a five-tier scale (pathogenic to benign) based on the actual weight of evidence for clinical significance, independent of population frequency alone, though frequency remains one input into that evidence
Clinical reports increasingly use "pathogenic variant" or "likely pathogenic variant" rather than "mutation," and "benign variant"/"likely benign variant" rather than "polymorphism," reflecting this more precise, evidence-graded terminology

ACMG/AMP variant classification framework, variants of uncertain significance, single nucleotide polymorphisms (SNPs) in population genetics/pharmacogenetics

Using "mutation" to mean "harmful" is imprecise and increasingly discouraged in clinical practice - a variant's clinical significance must be established through formal evidence-based classification, not assumed from the word used to describe it

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