Is CNOT1 p.Val2152= (c.6456G>A) pathogenic?

CNOT1 p.Val2152= (c.6456G>A) is classified Uncertain significance in CNOT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-02). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CNOT1 p.Val2152= (c.6456G>A)?

CNOT1 p.Val2152= (c.6456G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CNOT1 p.Val2152= (c.6456G>A) in the general population?

CNOT1 p.Val2152= (c.6456G>A) is absent from gnomAD v4.1 (gnomAD).

CNOT1 p.Val2152=

c.6456G>A · VCV3834552

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.72	acceptor gain · deltas
Pangolin	Δ0.26	gain · loss 0.09 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6	GERP 2.2, phastCons 1
Overall
CADD	21.9	PHRED · no single calibrated threshold — expert panels disagree

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: CNOT1
Protein: p.Val2152=
Coding: c.6456G>A
MANE Select: NM_016284
Type: single nucleotide variant
Location: chr16:58526136 (GRCh38)
Gene constraint: LOEUF 0.064 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.22 · 21 PDB
Residue 2152: an α-helix; a UniProt-annotated variant site (in vibos)

Full CNOT1 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

CNOT1 c.5895+4T>C Uncertain significance ★★ same condition
CNOT1 p.Ala1604Gly Uncertain significance ★★ ⚠ same condition
CNOT1 p.Arg211Cys Uncertain significance ★★ ⚠ same condition
CNOT1 p.Arg369Cys Uncertain significance ★★ ⚠ same condition
CNOT1 p.Asn1162Thr Uncertain significance ★★ ⚠ same condition
CNOT1 p.Asn1295Ser Uncertain significance ★★ ⚠ same condition
CNOT1 p.Asn2199Lys Uncertain significance ★★ ⚠ same condition
CNOT1 p.Asn349Ser 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/cnot1-p-val2152 (accessed [today's date]).

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