Is CNOT3 p.Arg389Trp (c.1165C>T) pathogenic?

CNOT3 p.Arg389Trp (c.1165C>T) is classified Uncertain significance in CNOT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.3073); Very rare (popmax 0.00948%, afr); Associated with Inborn genetic diseases.

What condition is associated with CNOT3 p.Arg389Trp (c.1165C>T)?

CNOT3 p.Arg389Trp (c.1165C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CNOT3 p.Arg389Trp (c.1165C>T) in the general population?

CNOT3 p.Arg389Trp (c.1165C>T) is very rare (popmax 0.00948%, afr) (gnomAD).

What do computational predictors say about CNOT3 p.Arg389Trp (c.1165C>T)?

AlphaMissense predicts likely benign (score 0.3073) — an in-silico prediction, not a clinical call.

CNOT3 p.Arg389Trp

c.1165C>T · rs745602918 · VCV2396143

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3073 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00948%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3073	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -10.45	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 0.85, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 7,004 bp · p 0.37 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00948% African / African-American · 7/73,802 alleles

Filtering AF 0.00443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00313%

Overall 0.003% 47/1,564,310 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00948%	10,543
European (non-Finnish)	0.00312%	32,038
East Asian	0.00226%	44,342
Admixed American	0.00181%	55,280
Finnishnot grpmax-eligible	0.00163%	61,360
South Asian	0.0012%	83,078

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.Arg389Trp
Coding: c.1165C>T
MANE Select: NM_014516
dbSNP: rs745602918
Type: single nucleotide variant
Location: chr19:54148418 (GRCh38)
Gene constraint: LOEUF 0.057 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.53 · 6 PDB
Residue 389: the 'disordered' region

Full CNOT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CNOT3 p.Arg389Gln Uncertain significance ★ ⚠ same residue
CNOT3 p.Ala438Val Uncertain significance ★★ ⚠ same condition
CNOT3 p.Arg290Cys Uncertain significance ★★ ⚠ same condition
CNOT3 p.Glu533Gln Uncertain significance ★★ ⚠ same condition
CNOT3 p.Gly405Ser Uncertain significance ★★ ⚠ same condition
CNOT3 p.Met182Val Uncertain significance ★★ ⚠ same condition
CNOT3 p.Pro244Ala Uncertain significance ★★ ⚠ same condition
CNOT3 p.Pro320Leu Uncertain significance ★★ ⚠ same condition

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-arg389trp (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown