EXOSC8 p.Pro69=
c.207A>G · rs2501602800 · VCV2995779
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.5e-05%, 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 1.1 | GERP 1, phastCons 1 |
| Overall | ||
| CADD | 10.34 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.5e-05%
European (non-Finnish) · 1/1,176,294 alleles
Overall
6.21e-05%
1/1,609,102 alleles · very rare
exomes 1/1,456,744 · genomes 0/152,358 · 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
- EXOSC8
- Protein
- p.Pro69=
- Coding
- c.207A>G
- MANE Select
- NM_181503
- dbSNP
- rs2501602800
- Type
- single nucleotide variant
- Location
- chr13:37004530 (GRCh38)
- Gene constraint
- LOEUF 1.944 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.77 · 8 PDB
- Residue 69
- an α-helix
Similar variants
- EXOSC8 p.Arg190Lys Uncertain significance ★★ ⚠ same type
- EXOSC8 p.Arg94Gln Uncertain significance ★★ ⚠ same type
- EXOSC8 p.Asp143Asn Uncertain significance ★★ ⚠ same type
- EXOSC8 p.Asp202Val Uncertain significance ★★ ⚠ same type
- EXOSC8 p.Ile170Val Uncertain significance ★★ ⚠ same type
- EXOSC8 p.Ile270Phe Uncertain significance ★★ ⚠ same type
- EXOSC8 p.Leu50Phe Uncertain significance ★★ same type
- EXOSC8 p.Thr71Ala 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/exosc8-p-pro69 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown