CNOT3 p.Thr670=
c.2010A>T · rs77902046 · VCV1598896
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 10.7%, eas) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.345 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -5.7 | GERP -2 |
| Overall | ||
| CADD | 1.69 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
10.7%
East Asian · 4,748/44,568 alleles
Filtering AF
10.4%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 10.3%
Overall
3.16%
50,746/1,604,432 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 10.7% | 9 |
| Finnishnot grpmax-eligible | 7.9% | 13 |
| South Asian | 5.6% | 18 |
| Ashkenazi Jewishnot grpmax-eligible | 4.88% | 20 |
| Admixed American | 3.82% | 26 |
| Remaining individualsnot grpmax-eligible | 3.1% | 32 |
| Middle Eastern | 2.58% | 39 |
| European (non-Finnish) | 2.54% | 39 |
| Amishnot grpmax-eligible | 2.32% | 43 |
| African / African-American | 0.375% | 266 |
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.Thr670=
- Coding
- c.2010A>T
- MANE Select
- NM_014516
- dbSNP
- rs77902046
- Type
- single nucleotide variant
- Location
- chr19:54152972 (GRCh38)
- Gene constraint
- LOEUF 0.057 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.53 · 6 PDB
- Residue 670
- the 'repressor domain' region; a UniProt-annotated variant site (in iddsadf); an α-helix
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-thr670 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown