Is CNOT2 p.Gln95= (c.285G>A) pathogenic?

CNOT2 p.Gln95= (c.285G>A) is classified Likely benign in CNOT2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-14). Very rare (popmax 8.48e-05%, nfe); Associated with CNOT2-related disorder.

What condition is associated with CNOT2 p.Gln95= (c.285G>A)?

CNOT2 p.Gln95= (c.285G>A) is associated with CNOT2-related disorder (ClinVar).

How common is CNOT2 p.Gln95= (c.285G>A) in the general population?

CNOT2 p.Gln95= (c.285G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

CNOT2 p.Gln95=

c.285G>A · rs2499098662 · VCV3058220

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

CNOT2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 0.86, phastCons 1
Overall
CADD	7.923	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,178,582 alleles

Overall 6.85e-05% 1/1,460,050 alleles · very rare

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: CNOT2
Protein: p.Gln95=
Coding: c.285G>A
MANE Select: NM_014515
dbSNP: rs2499098662
Type: single nucleotide variant
Location: chr12:70329469 (GRCh38)
Gene constraint: LOEUF 0.211 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 60.35 · 4 PDB

Full CNOT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CNOT2-related disorder

Similar variants

CNOT2 p.Asn14His Uncertain significance ★ ⚠ same condition
CNOT2 p.Ser90Asn Uncertain significance ⚠ same condition
CNOT2 p.Arg183Gln Uncertain significance ★★ ⚠ same type
CNOT2 p.Tyr494Cys Uncertain significance ★★ ⚠ same type
CNOT2 p.Gly32Glu Likely benign ★★ same type
CNOT2 p.Met49Val Likely benign ★★ same type
CNOT2 c.49-2A>G Likely pathogenic ★ same type
CNOT2 p.Ser228Ter Pathogenic ★ 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/cnot2-p-gln95 (accessed [today's date]).

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