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# Where new mutations come from: de novo variants, rates and parental age

Every child carries a few dozen DNA changes neither parent had; how often, where and in which parent they arise explains many sporadic genetic diseases.

Updated Nov 13, 2026

## Key facts

- The germline point-mutation rate is about 1 in 100 million bases per generation, so each newborn carries roughly 60–70 new single-base changes, usually one or none in a protein-coding region.
- Most new point mutations arise in the father: sperm precursors keep dividing throughout life, so the number of new mutations rises with paternal age.
- Some paternal-age disorders come from mutations that give sperm precursors a growth advantage (achondroplasia, Apert syndrome); they are almost always paternal in origin.
- Maternal age raises the risk of chromosome nondisjunction (trisomies), not of point mutations.
- Large genes have high new-mutation rates: about a third of Duchenne cases and about half of neurofibromatosis type 1 cases arise from new mutations.

## In detail

- Mutational hotspots: methylated cytosines in CpG pairs deaminate to thymine; repeated DNA segments misalign and recombine, producing recurrent deletions and duplications (22q11.2, 16p11.2).
- A mutation after fertilisation produces mosaicism: only some cells carry it. If it reaches the gonads (germline mosaicism), healthy parents can have more than one affected child.
- Somatic mutations accumulate in every tissue with age; they drive cancer and, in blood, clonal haematopoiesis.
- Each person differs from the reference genome at about 4–5 million positions; most variants are common and harmless, and everyone carries several recessive disease alleles.

**Also called**
De novo mutations, Paternal age effect

## Clinical notes

- When a dominant disorder appears in a child of healthy parents, a new mutation is the usual cause, but germline mosaicism keeps a small recurrence risk for siblings.
- Trio sequencing (child and both parents) finds de novo variants, a major cause of severe developmental disorders.

## Test yourself

Think of the answer, then tap the question to see it.

## Why do most new point mutations come from the father?

Sperm precursors divide continually through life, so more replication errors accumulate, and their number rises with paternal age.

## Why can two children of unaffected parents have the same «new» dominant mutation?

One parent can carry the mutation in part of the gonads (germline mosaicism) without being affected.

## Does advanced maternal age raise the risk of point mutations?

Mainly no; it raises the risk of chromosome nondisjunction and trisomies.

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## Connections

## Related conditions 4

- [Achondroplasia](https://durgical.com/en/conditions/achondroplasia/)
- [Duchenne muscular dystrophy](https://durgical.com/en/conditions/duchenne-muscular-dystrophy/)
- [Neurofibromatosis (types 1 and 2)](https://durgical.com/en/conditions/neurofibromatosis/)
- [Down syndrome (trisomy 21)](https://durgical.com/en/conditions/down-syndrome/)

## Related 5

- [Types of mutations](https://durgical.com/en/biochemistry/topics/types-of-mutations/)
- [DNA repair](https://durgical.com/en/biochemistry/topics/dna-repair/)
- [Genetic tests: what each one finds](https://durgical.com/en/biochemistry/topics/genetic-tests-what-each-one-finds/)
- [Population genetics: Hardy–Weinberg and carrier frequency](https://durgical.com/en/biochemistry/topics/population-genetics-hardy-weinberg-and-carrier-frequency/)
- [Trinucleotide repeat expansion disorders](https://durgical.com/en/biochemistry/topics/trinucleotide-repeat-expansion-disorders/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [What is a gene variant and how do variants occur?: MedlinePlus Genetics](https://medlineplus.gov/genetics/understanding/mutationsanddisorders/genemutation/) (MedlinePlus, US National Library of Medicine, 2026); [Mosaicism](https://www.genome.gov/genetics-glossary/Mosaicism) (National Human Genome Research Institute (NHGRI), 2026); [Copy Number Variation (CNV)](https://www.genome.gov/genetics-glossary/Copy-Number-Variation) (National Human Genome Research Institute (NHGRI), 2026); [Somatic Cells](https://www.genome.gov/genetics-glossary/Somatic-Cells) (National Human Genome Research Institute (NHGRI), 2026).

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/topics/where-new-mutations-come-from-de-novo-variants-rates-and-parental-age/