CNOT3 p.Pro244=
c.732C>A · rs762116071 · VCV2025305
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.01%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.193 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.64 | GERP -3.3, phastCons 0.01 |
| Overall | ||
| CADD | 5.705 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.01%
Admixed American · 6/59,998 alleles
Filtering AF
0.00428%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00295%
Overall
0.00136%
22/1,613,820 alleles · ultra-rare
exomes 20/1,461,646 · genomes 2/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.01% | 10,000 |
| African / African-American | 0.00267% | 37,461 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,476 |
| South Asian | 0.0011% | 91,082 |
| European (non-Finnish) | 0.00102% | 98,333 |
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.Pro244=
- Coding
- c.732C>A
- MANE Select
- NM_014516
- dbSNP
- rs762116071
- Type
- single nucleotide variant
- Location
- chr19:54145938 (GRCh38)
- Gene constraint
- LOEUF 0.057 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.53 · 6 PDB
- Residue 244
- the 'disordered' region
Similar variants
- CNOT3 p.Pro244Ala Uncertain significance ★★ ⚠ same residue
- CNOT3 p.Pro244Leu 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
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-pro244 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown