CNOT3 p.His709=
c.2127C>T · rs376265364 · VCV3250558
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
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 -11 | GERP -2 |
| Overall | ||
| CADD | 1.94 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.00347%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00229%
Overall
0.00279%
45/1,614,090 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| African / African-American | 0.00801% | 12,487 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,828 |
| South Asian | 0.00439% | 22,773 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,604 |
| European (non-Finnish) | 0.00254% | 39,335 |
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
- CNOT3
- Protein
- p.His709=
- Coding
- c.2127C>T
- MANE Select
- NM_014516
- dbSNP
- rs376265364
- Type
- single nucleotide variant
- Location
- chr19:54153804 (GRCh38)
- Gene constraint
- LOEUF 0.057 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.53 · 6 PDB
- Residue 709
- the 'repressor domain' region; a UniProt-annotated variant site (in iddsadf); a β-strand
Similar variants
- CNOT3 c.1904+2T>C Pathogenic/Likely pathogenic ★★ same type
- CNOT3 p.Arg697Ter Pathogenic ★★ same type
- CNOT3 p.Arg81Ser Likely pathogenic ★★ same type
- CNOT3 p.Arg96Ter Pathogenic/Likely pathogenic ★★ same type
- CNOT3 p.Thr86= Likely pathogenic ★★ same type
- CNOT3 c.1905-7C>G Uncertain significance ★★ same type
- CNOT3 c.483+6T>G Uncertain significance ★★ same type
- CNOT3 p.Ala376Thr 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/cnot3-p-his709 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown