INPP5E p.Pro526=
c.1578G>A · rs769912825 · VCV2193688
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0134%, eas)
Conditions
1
Joubert syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.57 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -2.7 |
| Overall | ||
| CADD | 0.852 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0134%
East Asian · 6/44,828 alleles
Filtering AF
0.00579%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00394%
Overall
0.00118%
19/1,612,832 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0134% | 7,471 |
| Finnishnot grpmax-eligible | 0.011% | 9,113 |
| African / African-American | 0.00268% | 37,339 |
| Admixed American | 0.00167% | 59,904 |
| European (non-Finnish) | 0.000254% | 393,190 |
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
- INPP5E
- Protein
- p.Pro526=
- Coding
- c.1578G>A
- MANE Select
- NM_015160 · reported on NM_019892
- dbSNP
- rs769912825
- Type
- single nucleotide variant
- Location
- chr9:136431089 (GRCh38)
- Structure
- AlphaFold pLDDT 88.46
Similar variants
- INPP5E p.Pro526Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- INPP5E p.Arg378Cys Pathogenic/Likely pathogenic ★★ same condition
- INPP5E p.Arg435Gln Pathogenic/Likely pathogenic ★★ same condition
- INPP5E p.Arg435Trp Pathogenic/Likely pathogenic ★★ same condition
- INPP5E p.Arg557His Pathogenic/Likely pathogenic ★★ same condition
- INPP5E p.Arg585Cys Pathogenic/Likely pathogenic ★★ same condition
- INPP5E p.Arg621Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
- INPP5E p.Arg621Trp Pathogenic/Likely pathogenic ★★ 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/inpp5e-p-pro526 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown