CCR5 rs333549: Understanding Genetic Factors in HIV Susceptibility
The rs333549 variant is located near the CCR5 gene, which encodes a critical protein used by HIV-1 to enter human immune cells. This variant is studied as a potential host genetic factor that may influence HIV acquisition and the progression of related disease.
What each genotype means
Common ancestral profile
You carry two copies of the C allele at this locus near CCR5. This genotype represents the ancestral background that is predominant in African lineages and common across worldwide populations. Because this variant primarily serves as an ancestry-informative genetic marker with limited direct functional consequence, carrying this genotype does not indicate any medical condition or alter your clinical care.
Found in over 90% of individuals of African ancestry and approximately 40% to 45% of individuals of European ancestry.
Single differentiated marker carrier
You carry one copy of the C allele and one copy of the T allele at this locus. This marker shows substantial population frequency differentiation between global groups, being relatively frequent in European lineages while rare in African lineages. Evidence of any direct phenotypic effect remains limited, and this result reflects historical population differentiation rather than a clinical health risk.
Carried by roughly 45% of individuals of European ancestry, but present in fewer than 10% of individuals of African ancestry.
Differentiated lineage marker
You carry two copies of the T allele at this marker near CCR5. Research indicates this allele expanded significantly in European-ancestry populations due to regional demographic and evolutionary histories. The current evidence does not associate this genotype with any actionable medical condition or altered drug metabolism.
Found in approximately 10% to 15% of individuals of European ancestry, and rarely observed (<1%) in individuals of African ancestry.
What is the rs333549 Variant?
The rs333549 variant is a single nucleotide polymorphism (SNP) situated in the genomic region surrounding the CCR5 gene. In genetics, a SNP represents a variation at a single position in a DNA sequence among individuals. While rs333549 is often discussed in the context of the well-known CCR5-Δ32 deletion, it is a distinct marker. Researchers study such variants to determine if they correlate with differences in how the body interacts with pathogens. Because this variant sits in a region involved in immune regulation, it has been a subject of interest for scientists investigating why individuals show different levels of susceptibility to viral infections, particularly HIV-1. It is important to note that rs333549 is a marker of genetic variation rather than a direct cause of disease, and its presence does not determine an individual's health outcome in isolation.
The Role of the CCR5 Gene
The CCR5 gene provides instructions for making a protein called C-C chemokine receptor type 5. This protein is found on the surface of certain white blood cells, including T cells, which are vital components of the immune system. Under normal conditions, the CCR5 protein acts as a receptor, helping the immune system respond to signals from other cells. However, HIV-1 exploits this protein as a 'co-receptor' to gain entry into and infect CD4+ T cells. Because of this, variations in the CCR5 gene or its regulatory regions can significantly alter the density of these receptors on cell surfaces. Research into these variations is essential for understanding the mechanisms of viral entry and the development of therapeutic strategies that aim to block the interaction between the virus and the host cell.
Research and Evidence Strength
The evidence linking rs333549 to specific clinical outcomes is currently considered limited. While the broader CCR5 locus is famously associated with HIV resistance—most notably through the CCR5-Δ32 deletion—the specific impact of the rs333549 SNP is less definitive. Some studies have explored its association with HIV-1 acquisition and disease progression, but results can be mixed or dependent on specific population backgrounds. It is crucial to distinguish between well-established genetic factors and those that require further validation. Because the immune system is highly complex and influenced by many genes, environmental factors, and viral strains, a single SNP rarely tells the whole story. Current research continues to evaluate how this variant might influence immune response, but it is not currently used as a standard diagnostic tool for predicting individual HIV risk or clinical prognosis.
Population Frequency
The frequency of genetic variants in the CCR5 region varies significantly across different ancestral groups. For rs333549, the minor allele frequency is approximately 0.35 in populations of European ancestry, while it is observed at a frequency of less than 0.05 in African ancestries. These differences highlight the importance of considering genetic diversity in medical research. Because variants like those in the CCR5 gene are not distributed uniformly, findings from one population cannot always be generalized to others. Understanding these frequency patterns helps scientists design more inclusive studies and interpret how genetic susceptibility might differ globally.
What This Information Means for You
Genetic information regarding variants like rs333549 is primarily intended for educational and research purposes. It is important to understand that having a particular genotype does not provide a medical diagnosis or a guarantee of health outcomes. If you are concerned about HIV risk, testing, or treatment, please consult with a qualified healthcare professional or an infectious disease specialist. They can provide guidance based on established clinical guidelines, which do not currently rely on this specific SNP for routine care. Never make changes to your health management or medication based on genetic data without consulting your clinician or pharmacist. Genetic research is an evolving field, and while it provides valuable insights into human biology, it is not a substitute for professional medical advice and standard clinical testing.
How common is this variant?
The minor allele frequency for rs333549 is approximately 0.35 in European ancestries and less than 0.05 in African ancestries.
Frequently asked questions
Does this variant mean I am immune to HIV?
No. This variant is not associated with total immunity to HIV. While some specific CCR5 mutations, such as the Δ32 deletion, are linked to reduced susceptibility, rs333549 does not confer such protection.
Should I get tested for this SNP?
There is no clinical recommendation to test for this SNP. It is primarily studied in research settings to understand immune function and is not used for routine medical diagnosis.
Can I use this information to change my medication?
No. You should never change your medication or treatment plan based on genetic information. Always discuss any questions about your health or medications with your doctor or pharmacist.
Why is the frequency different between populations?
Genetic variation is shaped by evolutionary history, migration, and natural selection over thousands of years. These factors lead to different frequencies of specific alleles in different ancestral groups.
Sources & further reading
Educational information only, last refreshed 10/21/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This promoter variant modulates CCR5 receptor expression levels on monocytes and is associated with susceptibility to inflammatory conditions like Löfgren’s syndrome, diabetic kidney disease, and recurrent pregnancy loss.
A 32-base pair deletion in the CCR5 gene that provides strong resistance to HIV-1 infection.