CNOT3 p.Ala240=
c.720C>T · VCV3697256
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0391%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.107 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.5 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 14.54 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0391%
European (non-Finnish) · 461/1,179,954 alleles
Filtering AF
0.0361%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.035%
Overall
0.0292%
471/1,613,622 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0391% | 2,560 |
| Finnishnot grpmax-eligible | 0.00628% | 15,935 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,822 |
| African / African-American | 0.00401% | 24,967 |
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.Ala240=
- Coding
- c.720C>T
- MANE Select
- NM_014516
- Type
- single nucleotide variant
- Location
- chr19:54145926 (GRCh38)
- Gene constraint
- LOEUF 0.057 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.53 · 6 PDB
- Residue 240
- the 'disordered' region
Similar variants
- CNOT3 p.Ala240Thr Uncertain significance ★ ⚠ same residue
- 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
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-ala240 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown