EXOSC3 p.Arg87=
c.261T>A · rs1294998925 · VCV1593622
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00161%, nfe)
Conditions
1
pontocerebellar hypoplasia type 1B
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 0.067 | GERP -3.1, phastCons 0.12 |
| Overall | ||
| CADD | 9.602 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00161%
European (non-Finnish) · 19/1,178,896 alleles
Filtering AF
0.00103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000831%
Overall
0.00118%
19/1,607,658 alleles · very rare
exomes 19/1,455,372 · genomes 0/152,286 · joint denominator
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
- EXOSC3
- Protein
- p.Arg87=
- Coding
- c.261T>A
- MANE Select
- NM_016042
- dbSNP
- rs1294998925
- Type
- single nucleotide variant
- Location
- chr9:37784784 (GRCh38)
- Gene constraint
- LOEUF 1.072 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 80.26 · 8 PDB
- Residue 87
- a β-strand
Similar variants
- EXOSC3 p.Arg186Ter Pathogenic/Likely pathogenic ★★ same condition
- EXOSC3 p.Asp132Ala Pathogenic ★★ same condition
- EXOSC3 p.Gly191Asp Likely pathogenic ★★ same condition
- EXOSC3 p.Gly31Ala Pathogenic/Likely pathogenic ★★ same condition
- EXOSC3 p.Met1Thr Pathogenic/Likely pathogenic ★★ same condition
- EXOSC3 p.Met1Val Pathogenic/Likely pathogenic ★★ same condition
- EXOSC3 p.Val80Phe Pathogenic/Likely pathogenic ★★ same condition
- EXOSC3 p.Ala139Pro Uncertain significance ★★ ⚠ same condition
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/exosc3-p-arg87 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown