NGF rs6330: What Your Genotype Means
The rs6330 variant is a missense single-nucleotide polymorphism located in the nerve growth factor (NGF) gene, also known as Ala35Val. It alters an amino acid in the pro-peptide sequence of the NGF precursor protein, which may modulate pro-NGF processing and signaling. Scientific research has linked rs6330 to subtle differences in stress response, autonomic nervous system regulation, and anxiety-related personality traits, though overall clinical evidence remains limited.
What each genotype means
Typical pro-NGF processing
You carry two copies of the C allele encoding the alanine form of the nerve growth factor pro-peptide. Published research indicates limited, sex-specific associations with anxiety traits, with some studies observing slightly higher trait anxiety in females but lower trait anxiety in males carrying this genotype. Because findings are mixed and based on limited observational evidence, this genotype does not determine stress resilience or clinical anxiety.
Carried by approximately 35% to 40% of individuals of European ancestry and roughly 45% to 50% globally, representing the most common genotype.
Intermediate pro-NGF processing
You carry one copy of the C allele and one copy of the T allele encoding the Ala35Val substitution in nerve growth factor. Research suggests an intermediate autonomic stress adaptation and variable, sex-dependent patterns in anxiety-related personality traits. Scientific evidence remains limited and observational, meaning carrying one copy of each allele does not reliably predict your psychological stress response.
Carried by roughly 45% to 50% of people of European descent and around 40% to 45% across broader global populations.
Altered pro-NGF processing
You carry two copies of the T allele encoding the valine form (p.Ala35Val) of nerve growth factor, which affects intracellular processing of the pro-peptide. Studies have linked this genotype to sex-specific stress vulnerability, including reports of higher anxiety traits in males and altered autonomic vagal tone, though effects in females are less pronounced. Evidence remains limited and non-diagnostic, so this genotype does not signify an anxiety disorder or autonomic impairment.
Carried by approximately 10% to 15% of people of European ancestry and less than 10% in many East Asian populations.
Genomic Location and Molecular Mechanism
The single-nucleotide polymorphism rs6330 resides on human chromosome 1 within exon 3 of the NGF gene. At the nucleotide level, this variation represents a cytosine-to-thymine transition (c.104C>T, often documented as G>A on the reverse complement strand). This change substitutes the amino acid alanine with valine at position 35 of the pro-domain precursor protein (Ala35Val). Because this substitution occurs in the pro-peptide region rather than the mature neurotrophin domain, researchers hypothesize that it subtly influences intracellular protein folding, cleavage efficiency, and secretion dynamics. In neurobiology, the uncleaved precursor pro-NGF binds preferentially to the p75 neurotrophin receptor (p75NTR) to promote pro-apoptotic or stress-related signaling, whereas mature NGF binds the high-affinity TrkA receptor (NTRK1) to support neuronal survival. Consequently, alterations in pro-peptide processing can alter the ratio of mature neurotrophin to pro-neurotrophin in neural circuits.
Biological Role of the NGF Gene
The NGF gene encodes nerve growth factor beta, an essential signaling protein belonging to the neurotrophin family. NGF plays a foundational role in the survival, differentiation, and maintenance of sympathetic and sensory neurons, particularly those responsible for nociception, temperature detection, and autonomic tone. Beyond basic structural neurodevelopment, NGF operates dynamically in the central nervous system, where it interacts with the hypothalamic-pituitary-adrenal (HPA) axis and limbic regions that orchestrate responses to acute and chronic stress. Elevated or perturbed NGF signaling has been observed during periods of psychological stress, social disruption, and inflammatory challenge. By regulating synaptic plasticity and autonomic output—such as heart rate variability and vagal modulation—NGF helps calibrate how an individual’s nervous system adapts to environmental stressors.
Scientific Research on Stress and Anxiety
A range of candidate-gene association studies have evaluated rs6330 in the context of affective regulation, anxiety-related personality traits, and autonomic adaptation. Some published studies have reported sex-dependent associations with trait anxiety, where carrying specific alleles coincided with elevated self-reported anxiety scores or altered cardiac vagal modulation under physiological challenges. Other investigative cohorts have examined rs6330 alongside other neurotrophin markers, such as BDNF Val66Met, evaluating risk burdens in psychiatric contexts or therapeutic outcomes in pediatric anxiety. However, the existing scientific evidence is classified as limited. Findings across independent cohorts have been mixed, with small sample sizes and variable effect directions depending on sex and demographic factors. rs6330 has not achieved genome-wide significance in large-scale psychiatric or psychological trait meta-analyses, indicating that its influence on complex behavioral phenotypes is at most modest.
Population Frequency and Demographics
Unlike rare pathogenic mutations in NGF that cause severe hereditary sensory and autonomic neuropathies, rs6330 is a very common polymorphism found across diverse global populations. In European ancestries cataloged in genomic databases such as gnomAD and 1000 Genomes, the minor allele occurs at an estimated frequency of approximately 0.30 to 0.38. This means that a substantial fraction of individuals carry at least one copy of the variant allele. Because of its high prevalence and benign classification in clinical databases such as ClinVar, rs6330 represents common normal human genetic diversity rather than a disease-causing mutation.
Practical Interpretation and Limitations
Genetic results for rs6330 cannot diagnose any mental health condition, predict an individual's specific stress tolerance, or direct psychiatric treatment choices. Complex traits like stress adaptation, anxiety, and autonomic regulation are polygenic and heavily influenced by life experience, developmental background, physical health, sleep quality, and social support. No clinical body or pharmacogenomic consortium recommends modifying clinical care or medication based on rs6330 genotype status. Readers should view rs6330 as an interesting window into basic neurotrophin biology rather than an actionable health indicator. If you are experiencing symptoms of stress or anxiety, speak with a qualified mental health clinician or healthcare provider.
How common is this variant?
The rs6330 minor allele frequency is approximately 0.31 globally and roughly 0.38 in European populations according to gnomAD data, making heterozygotes and homozygotes common worldwide.
Frequently asked questions
What is the NGF rs6330 variant?
rs6330 is a common missense variant in the nerve growth factor (NGF) gene, changing amino acid 35 from alanine to valine in the protein's pro-peptide sequence. Researchers study it to understand how natural variations in neurotrophin processing might influence the nervous system.
Does having the rs6330 variant mean I will have an anxiety disorder?
No. rs6330 is a common variation found in millions of healthy individuals and does not cause or diagnose anxiety disorders. Psychiatric and emotional traits are shaped by hundreds of genetic factors working together alongside lifestyle, environment, and personal history.
How does rs6330 affect the body biologically?
The variant sits in the pro-domain of the NGF precursor molecule, which is cleaved before mature NGF is released. Laboratory studies suggest it may subtly affect how efficiently pro-NGF is cleaved into mature NGF, potentially modulating signals between nerve cells.
Can I use my rs6330 genotype to pick medications or supplements?
No, rs6330 has no validated pharmacogenomic utility, and professional guidelines do not support using it to select drugs or supplements. Any questions regarding medications, dosing, or mental health management should always be discussed with a doctor or pharmacist.
Sources & further reading
Educational information only, last refreshed 9/10/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs6330?
Upload a raw DNA file from 23andMe, AncestryDNA, MyHeritage, or FamilyTreeDNA and see this variant — plus thousands more — interpreted in your full report.
Get my report — $29