INPP5E p.Arg396=
c.1188C>G · rs1206812099 · VCV1904907
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Conditions
1
Joubert syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.21 | acceptor loss, 13 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.5 | GERP 0.3, phastCons 1 |
| Overall | ||
| CADD | 9.529 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,882 alleles
Overall
0.000137%
2/1,461,256 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,882 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,492 |
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.Arg396=
- Coding
- c.1188C>G
- MANE Select
- NM_015160 · reported on NM_019892
- dbSNP
- rs1206812099
- Type
- single nucleotide variant
- Location
- chr9:136433047 (GRCh38)
- Structure
- AlphaFold pLDDT 88.46
Similar variants
- PMPCA p.Ala396Thr 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
- 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-arg396 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown