EXOSC2 p.Cys240=
c.720C>T · rs761749250 · VCV2019360
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
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 -4.5 |
| Overall | ||
| CADD | 5.679 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,018 alleles
Overall
0.000124%
2/1,613,996 alleles · very rare
exomes 2/1,461,682 · genomes 0/152,314 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,018 |
| African / African-American | 0.00133% | 75,038 |
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.Cys240=
- Coding
- c.720C>T
- MANE Select
- NM_014285
- dbSNP
- rs761749250
- Type
- single nucleotide variant
- Location
- chr9:130703100 (GRCh38)
- Gene constraint
- LOEUF 1.009 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.25 · 8 PDB
- Residue 240
- an α-helix
Similar variants
- EXOSC2 p.Cys240Ser Uncertain significance ★ same residue
- EXOSC2 p.Cys240Tyr Uncertain significance ★ ⚠ same residue
- 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
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-cys240 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown