30374e3fc3390902c35bb463510567f1b6f7a96e
lrnassar
Wed Apr 22 13:44:44 2026 -0700
PrimateAI-3D: clarify origin of the 0.821 threshold per Max. refs #37274
Description previously juxtaposed the paper's 0.821 clinical threshold
with the 75/25 benign/pathogenic split in a way that implied the two
were related. Per Max on the ticket: the 0.821 threshold comes from
Gao et al. 2023 Fig. 5A (calibrated against de novo missense excess
in a clinical cohort, n=7,238 pathogenic calls), and the "prediction"
column values are Illumina's own calls — not a simple application of
the 0.821 threshold (some variants below it are labeled pathogenic and
vice versa).
diff --git src/hg/makeDb/trackDb/human/primateAi.html src/hg/makeDb/trackDb/human/primateAi.html
index efbefed0947..7f4ea570c65 100644
--- src/hg/makeDb/trackDb/human/primateAi.html
+++ src/hg/makeDb/trackDb/human/primateAi.html
@@ -24,39 +24,46 @@
position sometimes produce the same amino acid change (codon degeneracy),
each item is labeled by default with its nucleotide change (e.g. C>T)
rather than its amino acid change. The label can be switched to the amino acid
change via the "Label fields" control in the Track Settings.
Hovering over a variant shows:
- Var — the nucleotide substitution on the + strand
(reference > alternate)
- AA — the resulting amino acid change
(single-letter reference > alternate)
- Score — the raw PrimateAI-3D pathogenicity score (0–1).
- The authors suggest a clinical threshold of 0.821 for distinguishing
- pathogenic from benign missense variants.
+ The authors suggest a clinical threshold of 0.821 for
+ distinguishing pathogenic from benign missense variants. This
+ threshold was calibrated against a subset of annotated mutations
+ in Gao et al. 2023 (Fig. 5A), chosen so that the number of
+ PrimateAI-3D pathogenic calls matched the observed excess of de
+ novo missense mutations in a clinical cohort (n = 7,238).
- Perc — the percentile rank of the raw score across all
scored variants (0–1). The track score field (0–1000) is this
value scaled by 1000.
- Pred — Illumina's binary call:
benign or
- pathogenic. In the track as
- distributed, about 75% of variants are benign and 25% are pathogenic.
+ pathogenic, as provided in the
+ source file. About 75% of variants in the track are benign and 25%
+ pathogenic. Note that this call is not a simple application
+ of the 0.821 raw-score threshold — some variants with raw
+ scores below 0.821 are labeled pathogenic and vice versa.
Items can be filtered by prediction (benign/pathogenic), by raw PrimateAI-3D
score, or by percentile.
Data Access
Due to the data license, the Table Browser, Data Integrator, and the REST API's
getData endpoint are disabled for this track. The source data can be
downloaded from the
PrimateAI-3D website
(requires registration). The primate variant database is available at
PrimAD.