EXOSC9 p.Ser306=
c.918G>A · rs145746159 · VCV1548369
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0617%, nfe)
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 -13 | GERP -3.7 |
| Overall | ||
| CADD | 1.203 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0617%
European (non-Finnish) · 728/1,179,594 alleles
Filtering AF
0.058%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0565%
Overall
0.0484%
781/1,613,428 alleles · ultra-rare
exomes 744/1,461,332 · genomes 37/152,096 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0617% | 1,620 |
| Remaining individualsnot grpmax-eligible | 0.048% | 2,082 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0203% | 4,932 |
| Admixed American | 0.0117% | 8,569 |
| African / African-American | 0.00801% | 12,477 |
| East Asian | 0.00223% | 44,856 |
| South Asian | 0.0022% | 45,535 |
| Finnishnot grpmax-eligible | 0.00156% | 64,004 |
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
- EXOSC9
- Protein
- p.Ser306=
- Coding
- c.918G>A
- MANE Select
- NM_005033
- dbSNP
- rs145746159
- Type
- single nucleotide variant
- Location
- chr4:121813324 (GRCh38)
- Gene constraint
- LOEUF 1.121 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.44 · 8 PDB
- Residue 306
- a UniProt-annotated variant site (in pch1d; reduced exosc9 and exosome levels in patient cells); a modified residue (phosphoserine)
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-ser306 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown