IPO8 p.Gln311=
c.933A>G · VCV3771707
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
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 -6.1 | GERP -4 |
| Overall | ||
| CADD | 0.534 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,054 alleles
Filtering AF
0.00583%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00242%
Overall
0.000187%
3/1,602,256 alleles · ultra-rare
exomes 3/1,449,958 · genomes 0/152,298 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,027 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,098 |
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.Gln311=
- Coding
- c.933A>G
- MANE Select
- NM_006390
- Type
- single nucleotide variant
- Location
- chr12:30671073 (GRCh38)
- Gene constraint
- LOEUF 0.575 · pLI 0.15 (gnomAD)
- Structure
- AlphaFold pLDDT 87.59
- Residue 311
- 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); a UniProt-annotated variant site (in viss)
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-gln311 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown