INPP5E p.Ala71=
c.213C>T · rs1281384783 · VCV2729315
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00389%, 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 0.51 | GERP -0.23, phastCons 0.8 |
| Overall | ||
| CADD | 6.803 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00389%
Admixed American · 2/51,450 alleles
Filtering AF
0.000645%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000241%
Overall
0.000195%
3/1,539,800 alleles · very rare
exomes 3/1,387,490 · genomes 0/152,310 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00389% | 25,725 |
| Remaining individualsnot grpmax-eligible | 0.00166% | 60,072 |
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.Ala71=
- Coding
- c.213C>T
- MANE Select
- NM_019892
- dbSNP
- rs1281384783
- Type
- single nucleotide variant
- Location
- chr9:136439207 (GRCh38)
- Structure
- AlphaFold pLDDT 88.46
Similar variants
- INPP5E p.Ala71Thr 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-ala71 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown