rs2476601
The autoimmunity variant that Europeans have and others do not
What this position does
PTPN22 sets the threshold at which immune cells activate. The variant version lowers it. It is a risk factor for rheumatoid arthritis, type 1 diabetes, lupus and several other autoimmune conditions, it is carried by roughly one European in ten, and it is essentially absent from East Asian and African populations. Whatever it was useful against, it is now a liability.
Immune system. Shaped by ancient infection, modern autoimmunity. This is one of the variants that differs sharply between human populations, because something in the environment made one version worth having.
Infection, and the cost of fighting it
For most of human history the commonest way to die young was infection. An immune system tuned to win those fights is tuned for a world that, in rich countries, no longer exists.
What changed: Industry, roughly the last two centuries. Indoor work, heated buildings, refined food, cheap salt and sugar, tobacco at scale, and a collapse in infectious disease. This is where most of the deals in your genome came undone.
Why it spread: nobody knows. The frequency difference between populations is real and measured. What the variant was worth having for is not known, and any site that tells you is guessing.
Spiral Staircase, chapter 18: The Immune System's Education Spiral Staircase is written by the same author as this site.
What each result means
| If you carry | What it means |
|---|---|
| No copies of the effect version GG | You do not carry it The common version on both copies, including for nearly everyone of East Asian or African descent. |
| One copy AG | You carry one copy Associated with roughly a doubled risk of rheumatoid arthritis and type 1 diabetes, from a low base. Most carriers never develop either. |
| Two copies AA | You carry two copies Uncommon. A higher risk again, still from a low base, and still not a prediction. |
How common each version is
| Ancestry group | A (the effect version) | |
|---|---|---|
| African | 0.3% | |
| American | 3.6% | |
| East Asian | 0.0% | |
| European | 9.4% | |
| South Asian | 1.3% |
1000 Genomes Project phase 3, via Ensembl, retrieved 2026-09-23. These groupings are coarse and flatten a great deal of internal diversity, particularly within Africa. A variant being common somewhere tells you where a piece of your ancestry probably comes from, and nothing else.
How many people carry each result
| Ancestry group | GG | AG | AA |
|---|---|---|---|
| African | 657 / 661 | 4 / 661 | 0 / 661 |
| European | 410 / 503 | 91 / 503 | 2 / 503 |
| East Asian | 504 / 504 | 0 / 504 | 0 / 504 |
| South Asian | 476 / 489 | 13 / 489 | 0 / 489 |
| American | 323 / 347 | 23 / 347 | 1 / 347 |
Counts of people, not modelled frequencies: every one of the 2,504 individuals sequenced by the 1000 Genomes Project phase 3, tallied by the genotype they carry. Deriving these from allele frequencies instead would assume random mating inside each group and undercount the homozygotes.
How to find out which you have
If you have taken a test with 23andMe, AncestryDNA, MyHeritage, Family Tree DNA, TellMeGen or Living DNA, this position is very likely already in the raw data file they gave you. You do not need another test.
One thing to watch if you look it up by hand: testing companies report some positions from one DNA strand and some from the other, and the file does not say which. Read the letters as they appear and you will get the opposite of the truth for some positions. Sequencings resolves that automatically.
Source
Coordinates and allele pair verified against Ensembl GRCh37. Direction of effect verified against VEP protein consequences or 1000 Genomes population frequency. Category: Population adaptation.
Where this fits
Common questions
What is rs2476601?
rs2476601 is a position in the PTPN22 gene on chromosome 1. PTPN22 sets the threshold at which immune cells activate. The variant version lowers it. It is a risk factor for rheumatoid arthritis, type 1 diabetes, lupus and several other autoimmune conditions, it is carried by roughly one European in ten, and it is essentially absent from East Asian and African populations. Whatever it was useful against, it is now a liability.
What does it mean if I have AA at rs2476601?
You carry two copies. Uncommon. A higher risk again, still from a low base, and still not a prediction.
What does it mean if I have GG at rs2476601?
You do not carry it. The common version on both copies, including for nearly everyone of East Asian or African descent.
How do I find out my rs2476601 genotype?
If you have taken a home DNA test, this position is very likely in the raw data file you were given. Sequencings reads that file in your browser without uploading it, and resolves which DNA strand each position was reported from, which is the step most manual lookups get wrong.
This is reference information, not medical advice, and not a diagnosis. See the medical disclaimer. Category: Population adaptation.