INPP5E p.Asp470=
c.1410T>C · rs138552060 · VCV1154913
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0217%, amr)
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 -2.4 | GERP -3 |
| Overall | ||
| CADD | 0.392 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0217%
Admixed American · 13/59,988 alleles
Filtering AF
0.0127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0101%
Overall
0.0018%
29/1,612,098 alleles · ultra-rare
exomes 18/1,460,246 · genomes 11/151,852 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0217% | 4,614 |
| East Asian | 0.00893% | 11,194 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,464 |
| European (non-Finnish) | 0.000933% | 107,236 |
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.Asp470=
- Coding
- c.1410T>C
- MANE Select
- NM_019892
- dbSNP
- rs138552060
- Type
- single nucleotide variant
- Location
- chr9:136431963 (GRCh38)
- Structure
- AlphaFold pLDDT 88.46
Similar variants
- INPP5E p.Asp470Asn 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-asp470 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown