Is CNOT9 p.Arg292Trp (c.874C>T) pathogenic?

CNOT9 p.Arg292Trp (c.874C>T) is classified Pathogenic in CNOT9 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-06-25). AlphaMissense: likely pathogenic (0.8452); Absent from gnomAD v4.1; Associated with CNOT9-related disorder.

What condition is associated with CNOT9 p.Arg292Trp (c.874C>T)?

CNOT9 p.Arg292Trp (c.874C>T) is associated with CNOT9-related disorder (ClinVar).

How common is CNOT9 p.Arg292Trp (c.874C>T) in the general population?

CNOT9 p.Arg292Trp (c.874C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNOT9 p.Arg292Trp (c.874C>T)?

AlphaMissense predicts likely pathogenic (score 0.8452) — an in-silico prediction, not a clinical call.

CNOT9 p.Arg292Trp

c.874C>T · rs981210817 · VCV1706475

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.8452 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CNOT9-related disorder

Computational evidence

Protein change
AlphaMissense	0.8452	likely pathogenic ✓ concordant with ClinVar
REVEL	0.248	benign-leaning
SaProt	LLR -10.08	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 0.77, phastCons 1
Regional constraint	o/e 0.36	constrained · MANE · 14 kb · p 7.3e-31 · regional, not allelic
Overall
CADD	24.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CNOT9
Protein: p.Arg292Trp
Coding: c.874C>T
MANE Select: NM_005444
dbSNP: rs981210817
Type: single nucleotide variant
Location: chr2:218594250 (GRCh38)
Gene constraint: LOEUF 0.523 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 92.83 · 14 PDB

Full CNOT9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CNOT9-related disorder

Similar variants

CNOT9 p.Arg227His Pathogenic/Likely pathogenic ★★ same condition
CNOT9 p.Arg46Gly Likely pathogenic ★ same condition
CNOT9 p.Pro131Leu Likely pathogenic ★ same condition
CNOT9 p.Ala101Thr Uncertain significance ★ ⚠ same condition
CNOT9 p.Arg46Gln Likely pathogenic ★ ⚠ same type
CNOT9 c.541-1G>T Uncertain significance ★ same type
CNOT9 p.Arg169Gln Uncertain significance ★ ⚠ same type
CNOT9 p.Arg227Pro 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/cnot9-p-arg292trp (accessed [today's date]).

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