Is CNOT9 p.Pro298Thr (c.892C>A) pathogenic?

CNOT9 p.Pro298Thr (c.892C>A) is classified Uncertain significance in CNOT9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-11). AlphaMissense: likely benign (0.0636); Absent from gnomAD v4.1.

How common is CNOT9 p.Pro298Thr (c.892C>A) in the general population?

CNOT9 p.Pro298Thr (c.892C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNOT9 p.Pro298Thr (c.892C>A)?

AlphaMissense predicts likely benign (score 0.0636) — an in-silico prediction, not a clinical call.

CNOT9 p.Pro298Thr

c.892C>A · VCV4685404

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0636 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,608,062)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0636	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -7.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.36	constrained · MANE · 14 kb · p 7.3e-31 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,608,062). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CNOT9
Protein: p.Pro298Thr
Coding: c.892C>A
MANE Select: NM_005444
Type: single nucleotide variant
Location: chr2:218594268 (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

Similar variants

CNOT9 p.Arg227His Pathogenic/Likely pathogenic ★★ same type
CNOT9 p.Arg292Trp Pathogenic ★★ ⚠ same type
CNOT9 p.Arg46Gln Likely pathogenic ★ ⚠ same type
CNOT9 p.Arg46Gly Likely pathogenic ★ same type
CNOT9 p.Pro131Leu Likely pathogenic ★ same type
CNOT9 c.541-1G>T Uncertain significance ★ same type
CNOT9 p.Ala101Thr Uncertain significance ★ ⚠ same type
CNOT9 p.Arg169Gln 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-pro298thr (accessed [today's date]).

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