IPO8 p.Leu190=
c.570T>C · rs147267141 · VCV2642813
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.558%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.6 | GERP -2.5, phastCons 1 |
| Overall | ||
| CADD | 8.664 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.558%
East Asian · 250/44,792 alleles
Filtering AF
0.501%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.479%
Overall
0.0173%
279/1,612,604 alleles · rare
exomes 222/1,460,302 · genomes 57/152,302 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.558% | 179 |
| Remaining individualsnot grpmax-eligible | 0.032% | 3,122 |
| South Asian | 0.00769% | 12,999 |
| Admixed American | 0.00167% | 59,994 |
| European (non-Finnish) | 8.48e-05% | 1,178,957 |
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
- IPO8
- Protein
- p.Leu190=
- Coding
- c.570T>C
- MANE Select
- NM_006390
- dbSNP
- rs147267141
- Type
- single nucleotide variant
- Location
- chr12:30680551 (GRCh38)
- Gene constraint
- LOEUF 0.575 · pLI 0.15 (gnomAD)
- Structure
- AlphaFold pLDDT 87.59
- Residue 190
- a UniProt-annotated variant site (in viss; undetectable protein levels in either patient's fibroblasts or patient's epstein-barr virus-immortalized b cell lines)
Similar variants
- IPO8 c.2900-1G>A Pathogenic/Likely pathogenic ★★ same type
- IPO8 p.Arg474Ter Pathogenic ★★ same type
- IPO8 p.Arg803Ter Pathogenic/Likely pathogenic ★★ same type
- IPO8 p.Trp259Ter Pathogenic ★★ same type
- IPO8 p.Ala877Asp Uncertain significance ★★ ⚠ same type
- IPO8 p.Ala941Val Uncertain significance ★★ ⚠ same type
- IPO8 p.Arg1002Trp Uncertain significance ★★ ⚠ same type
- IPO8 p.Arg884Gln Uncertain significance ★★ ⚠ same type
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/ipo8-p-leu190 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown