EXPLORATORY WORKING NOTE — not independently validated

This supplementary working library preserves submitted research for inspection and later correction. Earlier wording in a preserved page is subject to this correction ledger. Not medical advice.

Exploratory notes are published as working material for later refinement. Source status labels are historical; no independent validation is asserted. Raw API payloads are omitted.

A missing API field does not mean that medical evidence is absent; this is an audit of selected database fields.
support_n is an allele-record sample-support proxy, not a phenotype denominator, unique-person count, or effective sample size.
Sampling-noise and artefact conclusions are unsupported: this audit did not reconstruct the required denominators or propagate uncertainty.
The composite CPIC high-priority proportion measures a clinical-attention flag; it is not harm, adverse-reaction risk, or disease prevalence.
Older research-priority rankings and their figure/table are unvalidated. They must not be used as clinical or research-policy recommendations.

Manuscript exports: HTML, Markdown and DOCX are superseded v1 drafts; do not cite them as the corrected version. Data, figures and code retain their source values.

Exploratory research working note

ClinVar catalogue size for 21 actionable pharmacogenes

Question

How large is the ClinVar record catalogue for each of the 21 genes that carry an actionable CPIC recommendation? This is a measure of catalogued variation and curation attention, not of the number of pathogenic variants in a gene.

Method

Endpoint: NCBI E-utilities esearch, db=clinvar, retmode=json, retmax=0.
Query: <GENE>[gene] for each of 21 genes.
21 requests, 0.4 s apart, fetched 2026-10-30. Raw responses in raw.json.

Corrected scope

Version 1 reported a "pathogenic record" count using "pathogenic"[clinsig]. The E-utilities translation for that term is "pathogenic"[All Fields] — the clinical-significance field is not supported through this endpoint, so those counts were free-text matches, not significance-filtered records. That column has been removed rather than relabelled and published.

Results

Gene	ClinVar records
ABCG2	118
CACNA1S	3,592
CFTR	6,529
CYP2B6	131
CYP2C19	709
CYP2C9	104
CYP2D6	393
CYP3A5	111
CYP4F2	135
DPYD	760
G6PD	1,178
HLA-A	173
HLA-B	141
MT-RNR1	87
NAT2	150
NUDT15	99
RYR1	11,412
SLCO1B1	298
TPMT	74
UGT1A1	509
VKORC1	82

Findings

Catalogue size spans 154-fold, from TPMT (74) to RYR1 (11,412).
The three largest catalogues are RYR1 (11,412), CFTR (6,529) and CACNA1S (3,592).
A large catalogue is not evidence of clinical importance, and a small one is not evidence of safety: record counts track curation and submission behaviour.

What this does and does not show

It does not count pathogenic variants, individuals, or population frequencies.
ClinVar submissions are voluntary and skewed toward well-studied genes and large laboratories.
Record counts change as submitters reclassify; this is a single-day snapshot.
Gene-level totals mix variant types, including benign and uncertain records.

Reproduce

python3 code/fetch_clinvar.py   # writes raw.json and data.csv

Publication status

Blocker resolved by removing the unsupported claim (v2). Significance-filtered counts are not available through this endpoint; the note now reports catalogue size only. Ready for editorial review, not yet for publication.