IPO8 p.Ala519=
c.1557C>T · rs144184021 · VCV2578678
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.27%, eas)
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 0.48 | GERP -0.4, phastCons 0.99 |
| Overall | ||
| CADD | 7.66 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.27%
East Asian · 569/44,826 alleles
Filtering AF
1.18%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.15%
Overall
0.0375%
605/1,613,164 alleles · low-frequency
exomes 557/1,460,966 · genomes 48/152,198 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 1.27% | 79 |
| Remaining individualsnot grpmax-eligible | 0.0288% | 3,471 |
| Middle Eastern | 0.0165% | 6,060 |
| African / African-American | 0.00667% | 14,990 |
| Admixed American | 0.00167% | 59,936 |
| South Asian | 0.0011% | 90,872 |
| European (non-Finnish) | 0.000848% | 117,961 |
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.Ala519=
- Coding
- c.1557C>T
- MANE Select
- NM_006390
- dbSNP
- rs144184021
- Type
- single nucleotide variant
- Location
- chr12:30663526 (GRCh38)
- Gene constraint
- LOEUF 0.575 · pLI 0.15 (gnomAD)
- Structure
- AlphaFold pLDDT 87.59
- Residue 519
- 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); a UniProt-annotated variant site (in viss; undetectable protein levels in patient's fibroblasts, although mrna levels seem unaffected)
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-ala519 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown