INPP5E p.Arg557=
c.1671C>T · rs776792436 · VCV1090667
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00238%, 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 | Δ0.29 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.6 | GERP -2.7 |
| Overall | ||
| CADD | 12.07 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00238%
East Asian · 1/41,976 alleles
Filtering AF
8.2e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.5e-05%
Overall
0.000386%
6/1,555,514 alleles · very rare
exomes 6/1,403,152 · genomes 0/152,362 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00238% | 41,976 |
| South Asian | 0.00118% | 84,394 |
| European (non-Finnish) | 0.000348% | 287,181 |
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.Arg557=
- Coding
- c.1671C>T
- MANE Select
- NM_019892
- dbSNP
- rs776792436
- Type
- single nucleotide variant
- Location
- chr9:136430408 (GRCh38)
- Structure
- AlphaFold pLDDT 88.46
Similar variants
- INPP5E p.Arg557His Pathogenic/Likely pathogenic ★★ same residue
- INPP5E p.Arg557Cys 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.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-arg557 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown