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What is a missense variant?

A missense variant changes one amino acid in a protein. This guide explains what that means and how it differs from other variant types.

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Protein structure with one highlighted amino acid substitution in a bright molecular workspace.

A missense variant is a DNA change that swaps one amino acid in a protein. The protein is still made, but one building block is different.

What changes

DNA is read in three-letter codons. Each codon usually maps to one amino acid. If a variant changes a codon so it points to a different amino acid, the result is a missense variant.

The effect depends on where the amino acid sits in the protein and how different the replacement is. Some missense variants have little or no effect. Others can change folding, binding, stability, enzyme activity, or interactions with other proteins.

How it differs from other variants

Intronic variant: occurs outside the protein-coding exon sequence. Some intronic variants affect splicing, but many do not change the protein directly.
Synonymous variant: changes a DNA codon without changing the amino acid.
Stop gained variant: creates an early stop signal, which can shorten the protein.
Frameshift variant: insertion or deletion changes the reading frame, often altering the rest of the protein sequence.

How to review one

For a missense variant, check allele frequency, ClinVar status, affected protein domain, inheritance, genotype quality, and predictor scores such as AlphaMissense, REVEL, SIFT, or PolyPhen. No single score is enough by itself.