CNOT1 p.Glu1124=
c.3372A>G · rs770017454 · VCV2795445
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000424%, 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 · T>A here scores Δ0.40 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.6 | GERP 2.2, phastCons 1 |
| Overall | ||
| CADD | 13.51 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000424%
European (non-Finnish) · 5/1,179,970 alleles
Filtering AF
0.000124%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9e-05%
Overall
0.000342%
5/1,461,706 alleles · very rare
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.Glu1124=
- Coding
- c.3372A>G
- MANE Select
- NM_016284
- dbSNP
- rs770017454
- Type
- single nucleotide variant
- Location
- chr16:58549869 (GRCh38)
- Gene constraint
- LOEUF 0.064 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.22 · 21 PDB
- Residue 1124
- an α-helix; a UniProt-annotated variant site (in vibos); the 'interaction with cnot6, cnot6l, cnot7 and cnot8' region
Similar variants
- 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
- CNOT1 p.Ala1604Gly 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-glu1124 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown