INPP5E p.Lys4=
c.12G>A · rs962718636 · VCV2055361
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000807%, nfe)
Conditions
1
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 2 | GERP -0.27, phastCons 0.39 |
| Overall | ||
| CADD | 7.598 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000807%
European (non-Finnish) · 9/1,115,042 alleles
Filtering AF
0.00038%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000275%
Overall
0.000614%
9/1,466,666 alleles · very rare
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.Lys4=
- Coding
- c.12G>A
- MANE Select
- NM_019892
- dbSNP
- rs962718636
- Type
- single nucleotide variant
- Location
- chr9:136439408 (GRCh38)
- Structure
- AlphaFold pLDDT 88.46
Similar variants
- INPP5E p.Lys4Gln Uncertain significance ★★ ⚠ same residue
- INPP5E p.Lys4Met Uncertain significance ★★ ⚠ same residue
- PMPCA p.Val4= Likely benign ★★ same residue
- PMPCA p.Val4Glu Uncertain significance ★ ⚠ 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
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-lys4 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown