CNOT4 p.Ala583Thr
c.1747G>A · VCV4230944
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0384%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.126 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.35 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.7, phastCons 1 |
| Regional constraint | o/e 0.70 | unconstrained · MANE · 843 bp · p 0.0099 · regional, not allelic |
| Overall | ||
| CADD | 23.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0384%
Admixed American · 23/59,906 alleles
Filtering AF
0.0262%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0222%
Overall
0.00294%
47/1,597,938 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0384% | 2,605 |
| South Asian | 0.0044% | 22,744 |
| African / African-American | 0.00401% | 24,945 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,189 |
| European (non-Finnish) | 0.00127% | 78,641 |
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
- CNOT4
- Protein
- p.Ala583Thr
- Coding
- c.1747G>A
- MANE Select
- NM_001190850
- Type
- single nucleotide variant
- Location
- chr7:135363947 (GRCh38)
- Gene constraint
- LOEUF 0.236 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 62.54 · 2 PDB
Similar variants
- CNOT4 p.Ala101Ser Uncertain significance ★ ⚠ same type
- CNOT4 p.Ala459Thr Uncertain significance ★ ⚠ same type
- CNOT4 p.Ala587Val Uncertain significance ★ same type
- CNOT4 p.Ala649Pro Uncertain significance ★ same type
- CNOT4 p.Ala669Thr Uncertain significance ★ same type
- CNOT4 p.Arg323Gln Uncertain significance ★ ⚠ same type
- CNOT4 p.Arg342His Uncertain significance ★ ⚠ same type
- CNOT4 p.Arg3Cys 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/cnot4-p-ala583thr (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown