CNOT3 p.Thr645=
c.1935G>A · rs202216847 · VCV3051327
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0528%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.027 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.23 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -0.6 | GERP -2.3, phastCons 0.001 |
| Overall | ||
| CADD | 9.756 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0528%
Middle Eastern · 3/5,684 alleles
Filtering AF
0.0144%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00765%
Overall
0.0027%
41/1,515,926 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0528% | 1,895 |
| South Asian | 0.00753% | 13,274 |
| African / African-American | 0.00709% | 14,112 |
| Remaining individualsnot grpmax-eligible | 0.00686% | 14,570 |
| European (non-Finnish) | 0.00205% | 48,711 |
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.Thr645=
- Coding
- c.1935G>A
- MANE Select
- NM_014516
- dbSNP
- rs202216847
- Type
- single nucleotide variant
- Location
- chr19:54152897 (GRCh38)
- Gene constraint
- LOEUF 0.057 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.53 · 6 PDB
- Residue 645
- a UniProt-annotated variant site (in iddsadf)
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-thr645 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown