EXOSC3 p.Ala8=
c.24G>T · rs755145404 · VCV387842
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0161%, afr)
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 -16 | GERP -3.1 |
| Overall | ||
| CADD | 0.335 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0161%
African / African-American · 12/74,744 alleles
Filtering AF
0.00923%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00723%
Overall
0.00075%
12/1,600,898 alleles · ultra-rare
exomes 6/1,448,642 · genomes 6/152,256 · 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.Ala8=
- Coding
- c.24G>T
- MANE Select
- NM_016042
- dbSNP
- rs755145404
- Type
- single nucleotide variant
- Location
- chr9:37785021 (GRCh38)
- Gene constraint
- LOEUF 1.072 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 80.26 · 8 PDB
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-ala8 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown