GNRHR rs193922615: Understanding the Genetic Variant
The rs193922615 variant is a specific genetic change located within the GNRHR gene. It is associated with normosmic congenital hypogonadotropic hypogonadism, a condition characterized by the body's inability to produce sufficient sex hormones due to signaling issues in the reproductive system.
What each genotype means
Typical GNRHR function
You carry two copies of the common reference allele for the GNRHR gene at this position. This genotype is associated with normal gonadotropin-releasing hormone receptor signaling and typical pubertal development. It does not carry the elevated risk for congenital hypogonadotropic hypogonadism linked to the rare missense variant.
Carried by more than 99.9% of individuals across all global populations.
Carrier of rare variant
You carry one copy of the rare pathogenic missense allele in the GNRHR gene. GNRHR-related congenital hypogonadotropic hypogonadism typically follows an autosomal recessive pattern of inheritance, meaning a single altered copy generally does not cause clinical symptoms on its own. However, carrying this variant means you could potentially pass it to biological offspring or have reproductive implications if paired with another altered allele.
Extremely rare, found in approximately 1 in 2,500 individuals of Non-Finnish European descent (allele frequency ~0.0002) and even less frequently in other ancestries.
High risk of hypogonadotropic hypogonadism
You carry two copies of the rare missense substitution in the GNRHR gene. Biallelic loss-of-function variants in GNRHR are strongly linked in clinical research to normosmic congenital hypogonadotropic hypogonadism, which can impair gonadotropin secretion and pubertal development. If you are experiencing symptoms or have family planning questions, a consultation with a clinical geneticist or endocrinologist can help contextualize your endocrine health.
Exceedingly rare in the general population, with an expected prevalence of fewer than 1 in several million individuals globally.
What is rs193922615?
The variant rs193922615 is a single nucleotide polymorphism (SNP) found within the GNRHR gene, which is located on chromosome 4. In genetics, a SNP represents a variation at a single position in the DNA sequence. This specific variant is classified as a missense substitution, meaning the change in the DNA code results in a different amino acid being incorporated into the protein structure. Because the GNRHR gene provides instructions for creating the gonadotropin-releasing hormone receptor, alterations in this sequence can potentially change how the receptor functions. Researchers track these variants to understand how they might influence biological processes, particularly those related to the endocrine system and reproductive development.
The Role of the GNRHR Gene
The GNRHR gene encodes the gonadotropin-releasing hormone receptor, a protein that sits on the surface of cells in the pituitary gland. This receptor acts as a critical switch in the reproductive axis. When gonadotropin-releasing hormone (GnRH) binds to this receptor, it triggers a cascade of signals that tell the pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These hormones are essential for the development and function of the gonads, which include the testes in males and the ovaries in females. By regulating the timing and amount of these hormones, the GNRHR protein ensures that puberty and reproductive functions proceed normally. Disruptions in this gene can impair the receptor's ability to bind to its hormone or transmit signals, leading to hormonal imbalances.
Research and Clinical Associations
Scientific research has linked variants in the GNRHR gene to normosmic congenital hypogonadotropic hypogonadism (nCHH). This condition occurs when the body fails to produce enough sex hormones, often resulting in delayed or absent puberty. The evidence for specific variants like rs193922615 is often described as limited, meaning that while the gene itself is well-established as a cause of nCHH, the clinical impact of every individual variant may not be fully characterized. Studies often observe that these variants act in an autosomal recessive manner, meaning an individual typically needs to inherit the variant from both parents to experience symptoms. Because clinical presentation can vary widely even among individuals with the same genotype, researchers emphasize that genetic findings should always be interpreted by a qualified medical professional in the context of a patient's overall health and symptoms.
Population Frequency
The frequency of the rs193922615 variant is quite low in the general population. According to data from the Genome Aggregation Database (gnomAD), the allele frequency is approximately 0.0002 in Non-Finnish European populations. This rarity suggests that the variant is not a common feature of the human genome but rather a specific, infrequent change. Because it is so rare, it is unlikely to be encountered by the average person. When such variants are identified, they are usually found in the context of clinical genetic testing for individuals who are already experiencing symptoms related to reproductive development or hormonal health.
Interpreting Genetic Information
Understanding your genetic information requires careful consideration. If you have received a report mentioning rs193922615, it is important to remember that a genetic variant is only one piece of a much larger biological puzzle. Genetic testing results should never be used to self-diagnose or make medical decisions without the guidance of a doctor or a genetic counselor. These professionals can help determine if a variant is clinically significant for your specific situation, as many variants have little to no impact on health. If you are concerned about reproductive health or puberty, consult with an endocrinologist who can provide appropriate testing and evidence-based care. Always discuss any potential treatments or medication adjustments with your clinician or pharmacist, as they are best equipped to manage your health based on your unique medical history.
How common is this variant?
The rs193922615 variant is rare, with an allele frequency of approximately 0.0002 in Non-Finnish European populations according to gnomAD.
Frequently asked questions
What is normosmic congenital hypogonadotropic hypogonadism?
It is a condition where the body does not produce enough sex hormones due to a failure in the signaling pathway between the brain and the reproductive system. 'Normosmic' means that the sense of smell is typically unaffected, distinguishing it from other forms of hypogonadism.
Does having this variant mean I will have health problems?
Not necessarily. Many genetic variants are benign, and even those associated with conditions often require specific inheritance patterns to cause symptoms. You should discuss any genetic findings with a healthcare provider to understand their relevance to your health.
How is GNRHR-related hypogonadism treated?
Treatment typically involves hormone replacement therapy to induce puberty and support reproductive function. A medical professional, such as an endocrinologist, will determine the appropriate treatment plan based on individual clinical needs.
Can I change my GNRHR genotype?
No, your genotype is determined at conception and cannot be changed. Genetic information is a permanent part of your biological makeup.
Sources & further reading
Educational information only, last refreshed 10/11/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This synonymous variant in the gonadotropin-releasing hormone receptor gene is studied for its potential role in modulating reproductive hormone responsiveness.
Gonadotropin-releasing hormone receptor variant associated with altered gonadotropin pulsatility and susceptibility to delayed puberty.
Recessive pathogenic missense variant in gonadotropin-releasing hormone receptor causing normosmic idiopathic hypogonadotropic hypogonadism and delayed puberty.
A missense variant (p.Gln106Arg) in the gonadotropin-releasing hormone receptor associated with normosmic congenital hypogonadotropic hypogonadism.
Common missense variant (p.Gln106Arg) in the gonadotropin-releasing hormone receptor associated with hypogonadotropic hypogonadism and delayed puberty when compound heterozygous.
Pathogenic missense variant disrupting GnRH binding in the pituitary gonadotropes, causing severe hypogonadotropic hypogonadism.