EXOSC9 p.Arg249=
c.747A>G · rs2476771577 · VCV3002891
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.29 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.6 | GERP -2.1, phastCons 1 |
| Overall | ||
| CADD | 8.768 | PHRED · no single calibrated threshold — expert panels disagree |
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
- EXOSC9
- Protein
- p.Arg249=
- Coding
- c.747A>G
- MANE Select
- NM_005033
- dbSNP
- rs2476771577
- Type
- single nucleotide variant
- Location
- chr4:121811591 (GRCh38)
- Gene constraint
- LOEUF 1.121 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.44 · 8 PDB
- Residue 249
- the 'are binding' region; a UniProt-annotated variant site (in pch1d; reduced exosc9 and exosome levels in patient cells); an α-helix
Similar variants
- EXOSC9 p.Arg161Ter Pathogenic/Likely pathogenic ★★ same type
- EXOSC9 p.Arg212Ter Pathogenic ★★ same type
- EXOSC9 p.Arg229Ter Pathogenic/Likely pathogenic ★★ same type
- EXOSC9 p.Leu14Pro Pathogenic/Likely pathogenic ★★ same type
- EXOSC9 p.Ser7Ter Pathogenic/Likely pathogenic ★★ same type
- EXOSC9 c.1157-172A>G Uncertain significance ★★ same type
- EXOSC9 p.Ala148Val Uncertain significance ★★ ⚠ same type
- EXOSC9 p.Ala387Gly 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/exosc9-p-arg249 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown