EXOSC2 p.Ala229=
c.687T>C · rs751012139 · VCV2184045
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00661%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>A here scores Δ1.00 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.7 | GERP -4.5 |
| Overall | ||
| CADD | 6.418 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00661%
European (non-Finnish) · 78/1,179,792 alleles
Filtering AF
0.00538%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00498%
Overall
0.00541%
79/1,461,376 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00661% | 15,126 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,492 |
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.Ala229=
- Coding
- c.687T>C
- MANE Select
- NM_014285
- dbSNP
- rs751012139
- Type
- single nucleotide variant
- Location
- chr9:130703067 (GRCh38)
- Gene constraint
- LOEUF 1.009 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.25 · 8 PDB
- Residue 229
- 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-ala229 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown