Is CNOT3 p.Ser294Arg (c.882T>G) pathogenic?

CNOT3 p.Ser294Arg (c.882T>G) is classified Uncertain significance in CNOT3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-12-31). AlphaMissense: likely pathogenic (0.9845); Absent from gnomAD v4.1; Associated with CNOT3-related disorder.

What condition is associated with CNOT3 p.Ser294Arg (c.882T>G)?

CNOT3 p.Ser294Arg (c.882T>G) is associated with CNOT3-related disorder (ClinVar).

How common is CNOT3 p.Ser294Arg (c.882T>G) in the general population?

CNOT3 p.Ser294Arg (c.882T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNOT3 p.Ser294Arg (c.882T>G)?

AlphaMissense predicts likely pathogenic (score 0.9845) — an in-silico prediction, not a clinical call.

CNOT3 p.Ser294Arg

c.882T>G · rs2517699553 · VCV3031034

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9845 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CNOT3-related disorder

Computational evidence

Protein change
AlphaMissense	0.9845	likely pathogenic
REVEL	0.247	benign-leaning
SaProt	LLR -7.58	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -3
Regional constraint	o/e 0.96	unconstrained · MANE · 7,004 bp · p 0.37 · regional, not allelic
Overall
CADD	17.66	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: CNOT3
Protein: p.Ser294Arg
Coding: c.882T>G
MANE Select: NM_014516
dbSNP: rs2517699553
Type: single nucleotide variant
Location: chr19:54146645 (GRCh38)
Gene constraint: LOEUF 0.057 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.53 · 6 PDB
Residue 294: the 'disordered' region

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

Disease context

CNOT3-related disorder

Similar variants

CNOT3 p.Ser294Cys Uncertain significance ★ ⚠ same residue
CNOT3 p.Glu710Lys Uncertain significance ★★ ⚠ same condition
CNOT3 c.703+1G>A Likely pathogenic ★ same condition
CNOT3 p.Arg57Gly Likely pathogenic ★ same condition
CNOT3 p.Gln61Ter Likely pathogenic ★ same condition
CNOT3 p.Gly406Ter Likely pathogenic ★ same condition
CNOT3 p.Tyr648Ter Likely pathogenic ★ same condition
CNOT3 p.Glu143Ala 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-ser294arg (accessed [today's date]).

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