EXOSC2 p.Ile83=
c.249C>T · rs1006440166 · VCV1152136
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00322%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.26 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.1 | GERP -4.1, phastCons 0.003 |
| Overall | ||
| CADD | 11.71 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00322%
European (non-Finnish) · 38/1,179,958 alleles
Filtering AF
0.00239%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0021%
Overall
0.0026%
42/1,613,920 alleles · very rare
exomes 39/1,461,754 · genomes 3/152,166 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00322% | 31,052 |
| African / African-American | 0.00267% | 37,456 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,480 |
| South Asian | 0.0011% | 91,082 |
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
- EXOSC2
- Protein
- p.Ile83=
- Coding
- c.249C>T
- MANE Select
- NM_014285
- dbSNP
- rs1006440166
- Type
- single nucleotide variant
- Location
- chr9:130697606 (GRCh38)
- Gene constraint
- LOEUF 1.009 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.25 · 8 PDB
- Residue 83
- the s1 motif domain
Similar variants
- EXOSC2 p.Arg181Trp Uncertain significance ★★ ⚠ same type
- EXOSC2 p.Arg236Trp Uncertain significance ★★ ⚠ same type
- EXOSC2 p.Arg238Gln Uncertain significance ★★ ⚠ same type
- EXOSC2 p.Arg238Trp Uncertain significance ★★ ⚠ same type
- EXOSC2 p.Arg285Cys Uncertain significance ★★ ⚠ same type
- EXOSC2 p.Arg62Thr Uncertain significance ★★ same type
- EXOSC2 p.Arg87Leu Uncertain significance ★★ ⚠ same type
- EXOSC2 p.Arg87Ter 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/exosc2-p-ile83 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown