IPO8 p.Trp259Ter
c.776G>A · rs2136163716 · VCV1047913
Pathogenic
Multiple submitters
Classification
Pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
2
IPO8-related aortopathy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 7 of 25 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Pangolin | Δ0.34 | loss · gain 0.01 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 40.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- IPO8
- Protein
- p.Trp259Ter
- Coding
- c.776G>A
- MANE Select
- NM_006390
- dbSNP
- rs2136163716
- Type
- single nucleotide variant
- Location
- chr12:30674707 (GRCh38)
- Gene constraint
- LOEUF 0.575 · pLI 0.15 (gnomAD)
- Structure
- AlphaFold pLDDT 87.59
- Residue 259
- 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 condition
- IPO8 p.Arg474Ter Pathogenic ★★ same condition
- IPO8 p.Arg803Ter Pathogenic/Likely pathogenic ★★ same condition
- IPO8 p.Leu709Pro Uncertain significance ★★ ⚠ same condition
- IPO8 c.1428+5G>A Pathogenic ★ same condition
- IPO8 c.1756-1G>T Likely pathogenic ★ same condition
- IPO8 c.639+1G>A Pathogenic ★ same condition
- IPO8 p.Arg234Ter 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/ipo8-p-trp259ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown