PREPL p.Pro111Gln
c.332C>A · rs369303884 · VCV2470299
Computational evidence
| Protein change | ||
| AlphaMissense | 0.182 | likely benign |
|---|---|---|
| REVEL | 0.115 | moderately benign-leaning |
| SaProt | LLR -6.30 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 8.7 | GERP 2.5, phastCons 1 |
| Regional constraint | o/e 1.29 | unconstrained · MANE · 25 kb · p 1e-15 · regional, not allelic |
| Overall | ||
| CADD | 27.5 | 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 P200Q vs ClinVar P111Q) — verify the residue.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.134% | 748 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,492 |
| European (non-Finnish) | 8.48e-05% | 1,179,503 |
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
- PREPL
- Protein
- p.Pro111Gln
- Coding
- c.332C>A
- MANE Select
- NM_001171613
- dbSNP
- rs369303884
- Type
- single nucleotide variant
- Location
- chr2:44343762 (GRCh38)
- Gene constraint
- LOEUF 1.247 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 82.46 · 2 PDB
- Residue 200 UniProt numbering
- a β-strand
Similar variants
- PREPL p.Pro111Leu Uncertain significance ★★ ⚠ same residue
- PREPL p.Pro111= Likely benign ★ same residue
- PREPL c.-29A>G Uncertain significance ★★ ⚠ same condition
- PREPL c.-49+1840C>T Uncertain significance ★★ ⚠ same condition
- PREPL p.Ala3Thr Uncertain significance ★★ ⚠ same condition
- PREPL p.Ala432Thr Uncertain significance ★★ ⚠ same condition
- PREPL p.Arg174Leu Uncertain significance ★★ ⚠ same condition
- PREPL p.Arg353His Uncertain significance ★★ ⚠ same condition
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/prepl-p-pro111gln (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown