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PIK3CA encodes the p110α catalytic subunit of phosphoinositide 3-kinase (PI3K), an enzyme that converts the membrane lipid PIP2 into PIP3, thereby activating signaling cascades such as the AKT-mTOR pathway that promote cell survival, proliferation, growth, and motility. It is among the most commonly mutated genes in cancer, and aberrant activation of PI3K signaling is a driving event in tumor development, with the gene implicated in cancers including cervical cancer. Because this pathway is central to tumor growth, it is a major target of cancer therapies, although drug-induced pathway activation can also contribute to treatment resistance.
This variant
PIK3CA encodes the p110alpha catalytic subunit of PI3K, whose activation of AKT-mTOR signaling promotes cell survival and proliferation and is a common oncogenic event in cancers including cervical cancer. Because PIK3CA-related disease stems from gain-of-function activation, this rare missense variant (p.Pro316Ser) remains a Variant of Uncertain Significance: it is absent from population databases, yet no reported cases, functional studies, or ClinVar classifications demonstrate whether it activates the pathway.
Transcript
NM_006218.3
HGVS · transcript:coding
NM_006218.3:c.946C>T
GRCh38
chr3:179203676 C>T
GRCh37
chr3:178921464 C>T
Variant of Uncertain Significance: with the ClinGen VCEP final-classification rules unavailable, generic ACMG/AMP 2015 was used; only PM2 (Supporting) was met (variant absent from gnomAD v2.1, v4.1, and gnomAD-Canada), which reaches no classification threshold.
Classification rationale
PM2VUS
PIK3CA c.946C>Tmissense
PM2 (Supporting): variant absent from gnomAD v2.1, v4.1, and gnomAD-Canada (0 alleles, within the <=1 occurrence ceiling). Overall classification: Variant of Uncertain Significance, because the single supporting PM2 criterion satisfies no benign or pathogenic combination threshold.
PM2→VUS
LYFE Sciences is an AI system, and it can make mistakes. Criteria
may be applied incorrectly, sources may be misread, and a confident-looking
classification can still be wrong. Double-check every criterion and
its underlying evidence before relying on any call.
Gene diagram
· NM_006218.3 · variants mapped to exon structure
PIK3CANM_006218.3
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in PIK3CA—click a row to locate it on the plot · use the link column to open its page
Protein
Location
Classification
Link
Applied criteria · 1 applied · 13 assessed
MetEvidence satisfies this criterion.
Not metEvaluated against available evidence; threshold not reached.
Not assessedApplies in principle, but no evidence was found to evaluate it.
N/ADoesn't apply to this variant type.
Applied · 1
Strength Supporting Moderate Strong Very strong
✓
PM2supportingPathogenic
Met (Supporting): 0 alleles across gnomAD v2.1, v4.1, and gnomAD-Canada, within the <=1 occurrence ceiling.
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. PIK3CA, the catalytic subunit of PI3-kinase, is frequently mutated in a diverse range of cancers including breast, endometrial and cervical cancers.
