HRAS rs398122809: Understanding This Rare Genetic Variant
The rs398122809 variant is a rare genetic alteration located within the HRAS gene. It is classified as pathogenic and is associated with Costello syndrome, a multisystemic developmental disorder.
What each genotype means
Heterozygous carrier status
This genotype indicates the presence of one copy of the insertion variant. Research associates this variant with Costello syndrome, a condition affecting development and growth; please consult with a medical geneticist to understand the clinical implications for your health.
This genotype is extremely rare in the general population.
Homozygous variant status
This genotype indicates the presence of two copies of the insertion variant. This variant is classified as pathogenic and is linked to Costello syndrome; it is important to discuss these findings with a healthcare professional or genetic counselor.
This genotype is exceptionally rare and is not typically observed in general population databases.
What is rs398122809?
The variant rs398122809 is a specific genetic change identified within the HRAS gene, located on chromosome 11. In genetic databases, this variant is often described as an insertion or duplication, specifically involving the sequence TCT. Because it occurs in a critical region of the gene, it is categorized as a pathogenic variant. This means that the presence of this specific change is known to disrupt the normal function of the HRAS protein. Unlike common single nucleotide polymorphisms (SNPs) that might be found in a large percentage of the population, rs398122809 is extremely rare. It is typically identified through clinical genetic testing when a healthcare provider suspects a specific underlying genetic condition based on a patient's physical or developmental characteristics.
The Role of the HRAS Gene
The HRAS gene provides instructions for making a protein called H-Ras, which acts as a molecular switch within cells. This protein is part of the RAS/MAPK signaling pathway, a critical communication system that tells cells when to grow, divide, or mature. When the H-Ras protein is functioning normally, it helps regulate these fundamental biological processes. However, when a pathogenic variant like rs398122809 occurs, it can cause the H-Ras protein to remain in an 'always-on' state. This constant activation disrupts the delicate balance of cell signaling, which can lead to the developmental and physical features observed in conditions known as RASopathies. Because this pathway is involved in so many different tissues, variants in HRAS can affect multiple organ systems throughout the body.
Research and Clinical Associations
Scientific research has firmly established a link between pathogenic HRAS variants and Costello syndrome. Costello syndrome is a rare, multisystemic disorder characterized by features such as distinctive craniofacial appearance, cardiac abnormalities, developmental delays, and an increased predisposition to certain types of cancer, such as rhabdomyosarcoma and neuroblastoma. The evidence for the pathogenicity of variants in this gene is strong, as they are consistently identified in individuals who meet the clinical criteria for the syndrome. While the majority of these cases occur as de novo mutations—meaning they are not inherited from parents—there are rare instances of vertical transmission. Because of the complexity of these conditions, clinical diagnosis relies on a combination of physical examination and molecular genetic testing to confirm the presence of a pathogenic variant.
Population Frequency
The rs398122809 variant is considered extremely rare in the general population. It is not a common polymorphism that would be expected to appear in standard population screening datasets at any significant frequency. Because it is associated with a specific, rare clinical syndrome, its presence is almost exclusively documented in clinical settings rather than in large-scale, healthy population cohorts. Most individuals do not carry this variant.
Navigating Genetic Information
If you or a family member have received information about this variant, it is important to understand that this is a clinical finding that requires professional interpretation. Genetic variants associated with rare syndromes are not the same as common health-predisposition markers found in direct-to-consumer ancestry tests. This information should be discussed with a board-certified genetic counselor or a medical geneticist who can provide context based on individual clinical history. You cannot 'manage' this variant through lifestyle changes or supplements; rather, the focus is on clinical surveillance and supportive care managed by a multidisciplinary medical team. Always rely on your healthcare provider to explain what these results mean for your specific health situation and to guide any necessary follow-up care or diagnostic testing.
How common is this variant?
The rs398122809 variant is extremely rare and is not found at significant frequencies in general population databases.
Frequently asked questions
What is Costello syndrome?
Costello syndrome is a rare genetic disorder caused by mutations in the HRAS gene. It affects many parts of the body and is characterized by developmental delays, heart issues, and an increased risk of certain tumors.
Is rs398122809 inherited?
In most cases, this variant occurs as a de novo mutation, meaning it is not inherited from either parent. However, there are very rare reports of it being passed down in families.
Can I test for this variant at home?
No, this variant is typically identified through clinical-grade genetic testing ordered by a physician. Direct-to-consumer tests are generally not designed to detect or interpret rare, pathogenic variants of this nature.
What should I do if I have this variant?
If you have been informed that you or a family member carries this variant, you should consult with a medical geneticist or a genetic counselor. They can provide appropriate clinical guidance and coordinate necessary medical follow-up.
Sources & further reading
Educational information only, last refreshed 9/20/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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