BPI p.Arg194Gln
c.581G>A · VCV3481602
Computational evidence
| Protein change | ||
| AlphaMissense | 0.0774 | likely benign |
|---|---|---|
| REVEL | 0.075 | moderately benign-leaning |
| SaProt | LLR -8.79 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.27 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 0.27 | GERP -3.5 |
| Regional constraint | o/e 1.07 | unconstrained · MANE · 33 kb · p 0.094 · regional, not allelic |
| Overall | ||
| CADD | 3.85 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R198Q vs ClinVar R194Q) — verify the residue.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,625 |
| European (non-Finnish)grpmax | 0.00229% | 43,703 |
| East Asian | 0.00223% | 44,884 |
| South Asian | 0.0011% | 91,052 |
Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- BPI
- Protein
- p.Arg194Gln
- Coding
- c.581G>A
- MANE Select
- NM_001725
- Type
- single nucleotide variant
- Location
- chr20:38311918 (GRCh38)
- Gene constraint
- LOEUF 1.011 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.70 · 2 PDB
- Residue 194
- the 'n-terminal barrel' region; an α-helix; a disulfide bond
Similar variants
- BPI c.664+7G>T Benign ★★ same type
- BPI p.Ala12Val Benign ★★ same type
- BPI p.Ala192Val Benign ★★ same type
- BPI p.Ala333Thr Likely benign ★★ ⚠ same type
- BPI p.Ala8Thr Benign ★★ same type
- BPI p.Ala8Val Benign ★★ same type
- BPI p.Arg86Cys Benign ★★ ⚠ same type
- BPI p.Glu136Gln Benign ★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/bpi-p-arg194gln (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown