EXOSC9 p.Ala86=
c.258C>T · rs748226216 · VCV2998436
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00329%, sas)
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 -0.39 | GERP -3.8, phastCons 0.22 |
| Overall | ||
| CADD | 7.164 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00329%
South Asian · 3/91,064 alleles
Filtering AF
0.000875%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000443%
Overall
0.000479%
7/1,461,792 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00329% | 30,355 |
| East Asian | 0.00223% | 44,872 |
| African / African-American | 0.00133% | 75,002 |
| European (non-Finnish) | 0.000169% | 589,995 |
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.Ala86=
- Coding
- c.258C>T
- MANE Select
- NM_005033
- dbSNP
- rs748226216
- Type
- single nucleotide variant
- Location
- chr4:121802770 (GRCh38)
- Gene constraint
- LOEUF 1.121 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.44 · 8 PDB
- Residue 86
- the 'are binding' region; a turn
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-ala86 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown