Definition
Germline vs Somatic Variant
A germline variant is present in egg or sperm, is found in virtually every cell of the body and can be passed to children. A somatic variant arises after conception in some cells only, such as a tumor, and is not inherited.
1 min readReviewed September 14, 2026
Also known as: Hereditary vs acquired variant, Inherited vs acquired mutation, Germline mutation, Somatic mutation
Key facts
- Germline sample
- Usually blood or saliva
- Somatic sample
- Tumor tissue or circulating tumor DNA in blood
- Germline classification
- ACMG/AMP five-tier pathogenicity scheme
- Somatic classification
- AMP/ASCO/CAP Tiers I to IV; ClinGen/CGC/VICC oncogenicity
What are germline and somatic variants?
Germline variants are inherited from a parent or arise in a parent egg or sperm cell. Because they are present from conception, they appear in nearly every cell and can be passed to the next generation. Inherited cancer risk variants in BRCA1 and BRCA2 are germline variants.
Somatic variants are acquired during life, from DNA copying errors or environmental exposures such as ultraviolet light. They exist only in the cells descended from the cell where the change occurred and cannot be passed to children. Most variants that drive cancer growth are somatic.
How germline and somatic testing differ
The two kinds of testing answer different questions and use different methods:
- Germline testing looks for inherited risk and can have implications for blood relatives.
- Somatic, or tumor, testing looks for changes in the tumor that may guide treatment selection.
- Tumor testing can sometimes reveal a variant that is actually germline, but it does not replace dedicated germline testing.
- Tumor-normal testing sequences tumor and normal tissue together so germline and somatic variants can be separated.
- Mosaicism, where a variant is present in only some cells or tissues, blurs the line between the two categories.
Why the germline vs somatic distinction matters
The distinction determines which classification framework applies, which database fields to read and which patient population is being counted. Since January 2024, ClinVar has reported germline classifications separately from somatic clinical impact and oncogenicity classifications, so analyses that mix the fields can miscount.
For commercial teams, germline and somatic tests follow different ordering patterns, specialties and coverage rules. Medicare National Coverage Determination 90.2, for example, sets separate conditions for somatic and germline next-generation sequencing tests in cancer.