INPP5E p.Pro502=
c.1506G>A · rs74880446 · VCV365880
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 8 submitters
gnomAD v4.1
Rare
rare (popmax 0.139%, nfe)
Conditions
2
Joubert syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -7.9 | GERP -3 |
| Overall | ||
| CADD | 0.58 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.139%
European (non-Finnish) · 1,637/1,179,080 alleles
Filtering AF
0.133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.131%
Overall
0.116%
1,865/1,609,570 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.139% | 720 |
| Finnishnot grpmax-eligible | 0.0993% | 1,007 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0914% | 1,095 |
| Remaining individualsnot grpmax-eligible | 0.0849% | 1,177 |
| South Asian | 0.0529% | 1,892 |
| Middle Eastern | 0.0495% | 2,019 |
| Admixed American | 0.0285% | 3,509 |
| African / African-American | 0.0216% | 4,621 |
| East Asian | 0.00447% | 22,363 |
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.Pro502=
- Coding
- c.1506G>A
- MANE Select
- NM_015160 · reported on NM_019892
- dbSNP
- rs74880446
- Type
- single nucleotide variant
- Location
- chr9:136431867 (GRCh38)
- Structure
- AlphaFold pLDDT 88.46
Similar variants
- INPP5E p.Pro502Leu Uncertain significance ★★ ⚠ same residue
- PMPCA p.Thr502= Likely benign ★ 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.Arg563His Likely pathogenic ★★ ⚠ same condition
- INPP5E p.Arg585Cys 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-pro502 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown