EXOSC2 p.Gln291=
c.873G>A · rs34680820 · VCV1170769
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.6%, 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 6.6 | GERP 1.4, phastCons 1 |
| Overall | ||
| CADD | 8.183 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.6%
European (non-Finnish) · 30,678/1,179,304 alleles
Filtering AF
2.58%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.57%
Overall
2.11%
34,080/1,613,062 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 2.6% | 38 |
| Remaining individualsnot grpmax-eligible | 1.75% | 57 |
| Finnishnot grpmax-eligible | 1.71% | 58 |
| Admixed American | 0.695% | 144 |
| South Asian | 0.412% | 242 |
| Ashkenazi Jewishnot grpmax-eligible | 0.402% | 249 |
| African / African-American | 0.385% | 260 |
| Middle Eastern | 0.182% | 551 |
| East Asian | 0.00669% | 14,957 |
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
- EXOSC2
- Protein
- p.Gln291=
- Coding
- c.873G>A
- MANE Select
- NM_014285
- dbSNP
- rs34680820
- Type
- single nucleotide variant
- Location
- chr9:130703765 (GRCh38)
- Gene constraint
- LOEUF 1.009 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.25 · 8 PDB
- Residue 291
- an α-helix
Similar variants
- EXOSC2 p.Arg181Trp Uncertain significance ★★ ⚠ same type
- EXOSC2 p.Arg236Trp Uncertain significance ★★ ⚠ same type
- EXOSC2 p.Arg238Gln Uncertain significance ★★ ⚠ same type
- EXOSC2 p.Arg238Trp Uncertain significance ★★ ⚠ same type
- EXOSC2 p.Arg285Cys Uncertain significance ★★ ⚠ same type
- EXOSC2 p.Arg62Thr Uncertain significance ★★ same type
- EXOSC2 p.Arg87Leu Uncertain significance ★★ ⚠ same type
- EXOSC2 p.Arg87Ter 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/exosc2-p-gln291 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown