EXOSC3 p.Ala20=
c.60A>G · rs2489892482 · VCV2902172
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000509%, 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 -0.41 | GERP -0.42, phastCons 0.069 |
| Overall | ||
| CADD | 8.123 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000509%
European (non-Finnish) · 6/1,178,932 alleles
Filtering AF
0.000183%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00012%
Overall
0.000372%
6/1,611,400 alleles · very rare
exomes 6/1,459,048 · genomes 0/152,352 · 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.Ala20=
- Coding
- c.60A>G
- MANE Select
- NM_016042
- dbSNP
- rs2489892482
- Type
- single nucleotide variant
- Location
- chr9:37784985 (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 20
- 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-ala20 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown