What you carry at this position in your DNA and what research says about it.
Hemoglobin C Status: 10/10 evidence, 18 publications.
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Sample genotype (not yours): C/C
Typical Hemoglobin and Normal Malaria Susceptibility
Standard hemoglobin production ensures normal red blood cell structure and function. No elevated risk of hemolytic anemia or associated blood cell abnormalities is present.
What this genotype means: Normal red blood cell lifespan; Standard susceptibility to malaria.
Sample genotype (not yours): C/T
Malaria Resistance and Healthy Hemoglobin Carrier Status
Carrying one copy of the Hemoglobin C variant provides significant protection against malaria. Red blood cells function normally without causing anemia or other health complications.
What this genotype means: ~29% lower risk of clinical malaria; Asymptomatic carrier of Hemoglobin C.
Sample genotype (not yours): T/T
Strong Malaria Resistance with Mild Chronic Anemia
Two copies of the Hemoglobin C variant confer near-complete resistance to malaria. However, this state also causes mild chronic hemolytic anemia and an enlarged spleen.
What this genotype means: ~93% lower risk of clinical malaria; Mild chronic hemolytic anemia; Enlarged spleen (splenomegaly).
Gene function and biological role
Gene Function: The HBB gene encodes the beta-globin subunit of hemoglobin, the essential oxygen-carrying protein in red blood cells. Proper assembly of hemoglobin is critical for maintaining red blood cell structure and oxygen delivery throughout the body. Genetic variations in this gene can alter the physical properties of hemoglobin, leading to conditions like sickle cell disease or various forms of thalassemia. Interestingly, certain HBB variants have been maintained in human populations due to the survival advantage they confer against malaria.
Variant Impact: This missense variant, rs33930165, causes an amino acid substitution from glutamate to lysine at position 7 of the beta-globin protein, resulting in an abnormal hemoglobin variant known as Hemoglobin C. Unlike the more severe Hemoglobin S variant that causes sickle cell anemia, Hemoglobin C does not polymerize into rigid fibers under low oxygen conditions. Instead, it alters the physical properties of red blood cells, reducing their volume and increasing their density. This structural change makes the red blood cells less hospitable to malaria parasites, providing a natural defense mechanism.
Key Insight: Hemoglobin C provides a natural defense against malaria without causing the severe, painful complications associated with sickle cell anemia.
Location: HBB. Chromosome 11 · 11p15.4 · 5.2 Mb
Origin Story: The Hemoglobin C variant arose and was strongly selected for in West Africa, particularly in Burkina Faso, because it protects carriers against severe malaria while avoiding the high mortality associated with sickle cell disease.
Estimated prevalence by population
Global 99.3%; European 100.0%; African 97.3%; East Asian 100.0%; South Asian 100.0%; Americas 99.8%; Ashkenazi 100.0%; Finnish 100.0%; Middle Eastern 100.0%; Amish 100.0%.
Estimated CC genotype frequency.
Global 0.7%; European 0.0%; African 2.6%; East Asian 0.0%; South Asian 0.0%; Americas 0.2%; Ashkenazi 0.0%; Finnish 0.0%; Middle Eastern 0.0%; Amish 0.0%.
Estimated CT genotype frequency.
Global < 0.1%; European 0.0%; African < 0.1%; East Asian 0.0%; South Asian 0.0%; Americas < 0.1%; Ashkenazi 0.0%; Finnish 0.0%; Middle Eastern 0.0%; Amish 0.0%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Immunity & Inflammation
Infection Susceptibility & Resistance
Malaria Resistance. Evidence: 7/10. Source: PMID 11713529. Typical Risk.
Pneumonia. Evidence: 3/10. Source: PMID 39444160. Typical Risk.
Cardiovascular & Metabolic
Blood Cell & Iron Traits
Hemolytic Anemia. Evidence: 7/10. Source: PMID 23297836. No Risk.
Red Blood Cell Size. Evidence: 10/10. Source: PMID 32171239. Typical Volume.
Showing effects for C/T genotype
Malaria Resistance. Evidence: 7/10. Source: PMID 11713529. ~29% Lower Risk.
Pneumonia. Evidence: 3/10. Source: PMID 39444160. Slightly Increased.
Red Blood Cell Size. Evidence: 10/10. Source: PMID 32171239. Slightly Lower.
Showing effects for T/T genotype
Malaria Resistance. Evidence: 7/10. Source: PMID 11713529. ~93% Lower Risk.
Pneumonia. Evidence: 3/10. Source: PMID 39444160. ~4.4x Higher Risk.
Hemolytic Anemia. Evidence: 7/10. Source: PMID 23297836. Mild Chronic Anemia.
Red Blood Cell Size. Evidence: 10/10. Source: PMID 32171239. Significantly Lower.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Standard hemoglobin, known as Hemoglobin A, is produced by this genotype, ensuring that red blood cells remain flexible, round, and efficient at transporting oxygen. Because there are no altered hemoglobin variants present, there is no risk of developing Hemoglobin C-associated hemolytic anemia or splenomegaly. However, this typical structure does not provide any innate protection against malaria infection. Red blood cell indices, such as mean corpuscular volume and mean corpuscular hemoglobin concentration, remain within normal reference ranges. Overall, this genotype represents the baseline genetic profile for hemoglobin function across global populations.
Normal red blood cell lifespan; Standard susceptibility to malaria.
Sample genotype: CT (Heterozygous)
Production of both normal Hemoglobin A and the variant Hemoglobin C occurs in equal measure, a state known as Hemoglobin C trait. This combination alters the red blood cell membrane in a way that hinders the malaria parasite, Plasmodium falciparum, from properly presenting its adhesion proteins. Consequently, clinical malaria risk is reduced by approximately 29%. Because the normal hemoglobin copy compensates, there are no symptoms of anemia, and red blood cells maintain a healthy lifespan. This carrier status is entirely benign and does not require medical intervention or lifestyle adjustments.
~29% lower risk of clinical malaria; Asymptomatic carrier of Hemoglobin C.
Sample genotype: TT (Homozygous)
Exclusive production of Hemoglobin C leads to a condition known as Hemoglobin C disease. Red blood cells become smaller, denser, and more rigid, which triggers their premature destruction in the spleen. This accelerated clearance results in mild chronic hemolytic anemia and moderate splenomegaly. Remarkably, these cellular changes make it extremely difficult for malaria parasites to survive and multiply, reducing clinical malaria risk by up to 93%. While the anemia is typically mild and rarely requires treatment, it is associated with altered red blood cell indices and a higher susceptibility to infections like pneumonia.
~93% lower risk of clinical malaria; Mild chronic hemolytic anemia; Enlarged spleen (splenomegaly).
Variants with shared genetic architecture
rs11549407 · HBB Gene · Chr 11 · Thalassemia and Anemia Risk
rs33946267 · HBB Gene · Chr 11 · Hemoglobin D Disease Risk
rs334 · HBB Gene · Chr 11 · Sickle Cell Status
Content updated August 2026.
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