PPIB p.Glu183Ala
c.548A>C · rs369952028 · VCV1376786
Computational evidence
| Protein change | ||
| AlphaMissense | 0.6998 | likely pathogenic |
|---|---|---|
| REVEL | 0.676 | pathogenic-leaning |
| SaProt | LLR -13.06 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.8 | GERP 2.1, phastCons 1 |
| Regional constraint | o/e 0.98 | unconstrained · MANE · 6,960 bp · p 0.77 · regional, not allelic |
| Overall | ||
| CADD | 29.5 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0105% | 9,516 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,498 |
| African / African-American | 0.00267% | 37,461 |
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
- PPIB
- Protein
- p.Glu183Ala
- Coding
- c.548A>C
- MANE Select
- NM_000942
- dbSNP
- rs369952028
- Type
- single nucleotide variant
- Location
- chr15:64156126 (GRCh38)
- Gene constraint
- LOEUF 1.104 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 91.98 · 8 PDB
- Residue 183
- the ppiase cyclophilin-type domain; an α-helix
Similar variants
- PPIB p.Arg7Ser Uncertain significance ★★ ⚠ same condition
- PPIB p.Asn75Ser Uncertain significance ★★ ⚠ same condition
- PPIB p.Gly39Trp Uncertain significance ★★ ⚠ same condition
- PPIB p.Lys116Arg Uncertain significance ★★ ⚠ same condition
- PPIB p.Lys45Arg Uncertain significance ★★ ⚠ same condition
- PPIB p.Lys92Arg Uncertain significance ★★ ⚠ same condition
- PPIB p.Thr113Ile Uncertain significance ★★ ⚠ same condition
- PPIB p.Tyr88Cys 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/ppib-p-glu183ala (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown