PER2 rs121912442: Understanding the S662G Variant
The rs121912442 variant in the PER2 gene is a rare genetic change associated with Familial Advanced Sleep Phase Syndrome (FASPS-1). This condition causes individuals to have a stable, significantly earlier sleep-wake schedule than is typical for the general population.
What each genotype means
Typical circadian timing
You carry two copies of the standard allele and do not have the rare missense variant linked to familial advanced sleep phase syndrome 1. Research indicates that individuals with this genotype follow conventional population circadian rhythms and normal sleep-wake timing regulation by casein kinase phosphorylation. Your genetic risk for early sleep-phase shifts attributable to this specific locus is not elevated.
Carried by more than 99.99% of people worldwide across all major ancestral populations in gnomAD.
Advanced sleep phase syndrome
You carry one copy of the rare p.Ser662Gly alteration (c.1984A>G) in the PER2 gene, which is inherited in an autosomal dominant pattern. In published clinical pedigrees, heterozygous carriers display familial advanced sleep phase syndrome 1 (FASPS1), typically shifting sleep onset and morning awakening approximately 3 to 4 hours earlier than standard schedules. Because biological circadian rhythms such as core body temperature and melatonin release are phase-advanced, you may experience persistent early-evening sleepiness and early-morning waking.
Extremely rare; observed in private multi-generational kindreds and documented at a frequency under 0.01% in gnomAD.
Advanced sleep phase syndrome
You carry two copies of the pathogenic p.Ser662Gly alteration in the PER2 gene. Homozygous human carriers have rarely or never been documented in standard clinical literature because the condition displays autosomal dominant inheritance from a single variant allele. Mouse models homozygous for this mutation exhibit severe shortening of intrinsic circadian period length and markedly advanced behavioral rest-activity rhythms.
Extremely rare or undocumented in global reference populations such as gnomAD.
What is the rs121912442 Variant?
The variant rs121912442, often referred to as the Ser662Gly (S662G) mutation, is a specific change in the DNA sequence of the PER2 gene. Located on chromosome 2, this variant involves a single nucleotide substitution that results in the replacement of the amino acid serine with glycine at position 662 of the PER2 protein. This specific site is critical because it serves as a target for phosphorylation by casein kinase enzymes. When this site is altered, the normal regulatory processes that govern the protein's function are disrupted. Because this variant is extremely rare and typically identified within specific families, it is classified as a private familial variant rather than a common polymorphism found throughout the general population.
The Role of the PER2 Gene
The PER2 gene, which stands for Period Circadian Regulator 2, plays a fundamental role in maintaining the body's internal biological clock. It encodes a protein that acts as a transcriptional repressor, meaning it helps turn off the expression of certain genes in a rhythmic, 24-hour cycle. This process is essential for generating circadian rhythms, which regulate sleep-wake cycles, hormone release, and body temperature. The PER2 protein functions within a complex feedback loop where it is periodically modified by enzymes like casein kinase. This modification is necessary to control the stability and activity of the protein. By ensuring that the PER2 protein is degraded or activated at the correct time, the gene helps the body synchronize its internal processes with the external environment.
Research and Clinical Associations
Research has linked the S662G mutation to Familial Advanced Sleep Phase Syndrome (FASPS-1). Individuals with this condition experience a persistent, stable sleep schedule that is advanced by several hours compared to the conventional norm, often leading to very early evening sleep onset and early morning awakening. Scientific studies have demonstrated that the S662G mutation impairs the ability of casein kinase to phosphorylate the PER2 protein. This impairment leads to decreased protein stability and altered repressor activity, which effectively shortens the internal circadian period. While the evidence linking this specific variant to FASPS-1 is strong within the context of the families studied, it is important to note that FASPS is a rare condition. Other genetic factors and environmental influences can also contribute to sleep-wake phase disorders.
Population Frequency and Interpretation
The rs121912442 variant is exceptionally rare, with a frequency of less than 0.0001 in large-scale population databases like gnomAD. Because it is a private familial variant, it is not something typically encountered in the general population or standard genetic screening panels. If an individual is concerned about their sleep patterns, it is essential to understand that sleep disorders are complex and can be influenced by a wide variety of genetic and non-genetic factors. This information is for educational purposes only and should not be used for self-diagnosis. If you are experiencing persistent sleep difficulties that impact your daily life, you should consult with a healthcare professional or a sleep specialist to discuss your symptoms and appropriate clinical evaluation.
How common is this variant?
The rs121912442 variant is extremely rare in the general population, appearing with a frequency of less than 0.0001 in gnomAD, and is primarily identified as a private variant within specific families.
Frequently asked questions
What is Familial Advanced Sleep Phase Syndrome?
FASPS is a rare circadian rhythm disorder where individuals have a stable sleep schedule that is shifted several hours earlier than normal. People with this condition typically fall asleep in the early evening and wake up very early in the morning.
Can I get tested for the PER2 S662G variant?
Genetic testing for this specific variant is generally only performed in a clinical research context or through specialized genetic counseling for families with a known history of FASPS. It is not a standard test for general sleep complaints.
Is the PER2 S662G mutation the only cause of advanced sleep phase?
No, advanced sleep phase can be caused by mutations in several different genes, including PER3 and CSNK1D. Additionally, many people with advanced sleep phase may not have a single identifiable genetic mutation.
What should I do if I think I have a sleep disorder?
If you are concerned about your sleep patterns, you should consult a primary care physician or a sleep specialist. They can evaluate your symptoms and determine if a sleep study or further clinical investigation is necessary.
Sources & further reading
Educational information only, last refreshed 10/12/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This intronic variant in the PER2 gene is associated with individual differences in circadian rhythm, sleep timing, and chronotype.
Common missense/synonymous tagging variant in core clock gene PER2 modulating eveningness preference and diurnal phase delay.
Variant in the circadian regulator PER2 associated with circadian rhythm phase, chronotype, and timing of habitual sleep.
This variant is associated with familial advanced sleep phase syndrome, affecting the timing of the sleep-wake cycle.
A mutation in the PER2 gene associated with familial advanced sleep phase syndrome, leading to an earlier sleep-wake cycle.
An intronic single-nucleotide variant in the core clock gene PER2 recently identified in familial delayed sleep phase syndrome and evening chronotypes.