CNOT1 p.Ala2228=
c.6684G>A · VCV4780802
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0254%, afr)
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 -1.4 | GERP -4.9 |
| Overall | ||
| CADD | 9.977 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0254%
African / African-American · 19/74,888 alleles
Filtering AF
0.0166%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0137%
Overall
0.0018%
29/1,613,778 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0254% | 3,941 |
| East Asian | 0.00223% | 44,890 |
| Admixed American | 0.00167% | 59,990 |
| South Asian | 0.0011% | 91,070 |
| European (non-Finnish) | 0.000593% | 168,574 |
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
- CNOT1
- Protein
- p.Ala2228=
- Coding
- c.6684G>A
- MANE Select
- NM_016284
- Type
- single nucleotide variant
- Location
- chr16:58525279 (GRCh38)
- Gene constraint
- LOEUF 0.064 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.22 · 21 PDB
- Residue 2228
- an α-helix; a UniProt-annotated variant site (in vibos)
Similar variants
- CNOT1 p.Ala2228Val Uncertain significance ★ ⚠ same residue
- CNOT1 c.434-2A>G Pathogenic ★★ same type
- CNOT1 p.Arg26Ter Pathogenic/Likely pathogenic ★★ same type
- CNOT1 p.Arg535Cys Pathogenic ★★ same type
- CNOT1 c.310-3C>G Uncertain significance ★★ same type
- CNOT1 c.5895+4T>C Uncertain significance ★★ same type
- CNOT1 p.Ala1368Val Uncertain significance ★★ ⚠ same type
- CNOT1 p.Ala1503Thr 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/cnot1-p-ala2228 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown