EXOSC4 p.Gln75=
c.225A>G · rs111633196 · VCV774253
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.94%, mid)
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 0.33 | GERP -3.2, phastCons 0.96 |
| Overall | ||
| CADD | 6.292 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.94%
Middle Eastern · 57/6,062 alleles
Filtering AF
0.784%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.778%
Overall
0.661%
10,663/1,614,074 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.94% | 106 |
| European (non-Finnish) | 0.797% | 125 |
| Remaining individualsnot grpmax-eligible | 0.55% | 182 |
| Finnishnot grpmax-eligible | 0.346% | 289 |
| South Asian | 0.343% | 292 |
| Admixed American | 0.208% | 480 |
| East Asian | 0.163% | 615 |
| African / African-American | 0.128% | 782 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0844% | 1,184 |
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
- EXOSC4
- Protein
- p.Gln75=
- Coding
- c.225A>G
- MANE Select
- NM_019037
- dbSNP
- rs111633196
- Type
- single nucleotide variant
- Location
- chr8:144079996 (GRCh38)
- Gene constraint
- LOEUF 1.359 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.34 · 8 PDB
Similar variants
- EXOSC4 p.Ala159Val Uncertain significance ★ ⚠ same type
- EXOSC4 p.Ala197Thr Uncertain significance ★ ⚠ same type
- EXOSC4 p.Ala19Ser Uncertain significance ★ ⚠ same type
- EXOSC4 p.Ala203Thr Uncertain significance ★ ⚠ same type
- EXOSC4 p.Ala2Val Uncertain significance ★ ⚠ same type
- EXOSC4 p.Arg118His Uncertain significance ★ ⚠ same type
- EXOSC4 p.Arg204Gln Uncertain significance ★ same type
- EXOSC4 p.Arg222Gln 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/exosc4-p-gln75 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown