CNOT9 p.Arg227Pro
c.680G>C · VCV3343500
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9981 | likely pathogenic |
|---|---|---|
| REVEL | 0.786 | moderately pathogenic-leaning |
| SaProt | LLR -16.16 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Pangolin | Δ0.20 | loss · gain 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2, phastCons 1 |
| Regional constraint | o/e 0.36 | constrained · MANE · 14 kb · p 7.3e-31 · regional, not allelic |
| Overall | ||
| CADD | 33.0 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CNOT9
- Protein
- p.Arg227Pro
- Coding
- c.680G>C
- MANE Select
- NM_005444
- Type
- single nucleotide variant
- Location
- chr2:218592656 (GRCh38)
- Gene constraint
- LOEUF 0.523 · pLI 0.96 (gnomAD)
- Structure
- AlphaFold pLDDT 92.83 · 14 PDB
- Residue 227
- an α-helix
Similar variants
- CNOT9 p.Arg227His Pathogenic/Likely pathogenic ★★ same residue
- CNOT9 p.Arg227Ser Uncertain significance ★ ⚠ same residue
- CNOT9 p.Arg292Trp Pathogenic ★★ ⚠ same type
- CNOT9 p.Arg46Gln Likely pathogenic ★ ⚠ same type
- CNOT9 p.Arg46Gly Likely pathogenic ★ same type
- CNOT9 p.Pro131Leu Likely pathogenic ★ same type
- CNOT9 c.541-1G>T Uncertain significance ★ same type
- CNOT9 p.Ala101Thr 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/cnot9-p-arg227pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown