Is CNOT1 p.Glu1268fs (c.3802_3806del) pathogenic?

CNOT1 p.Glu1268fs (c.38023806del) is classified Likely pathogenic in CNOT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-09). Associated with CNOT1-related disorder.

What condition is associated with CNOT1 p.Glu1268fs (c.3802_3806del)?

CNOT1 p.Glu1268fs (c.3802_3806del) is associated with CNOT1-related disorder (ClinVar).

CNOT1 p.Glu1268fs

c.3802_3806del · VCV4930333

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

CNOT1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 28 of 49
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.12	GERP -1.2, phastCons 0.98

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: CNOT1
Protein: p.Glu1268fs
Coding: c.3802_3806del
MANE Select: NM_016284
Type: Deletion
Location: chr16:58546694 (GRCh38)
Gene constraint: LOEUF 0.064 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.22 · 21 PDB
Residue 1268: an α-helix; a UniProt-annotated variant site (in vibos); the 'interaction with cnot6, cnot6l, cnot7 and cnot8' region

Full CNOT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CNOT1-related disorder

Similar variants

CNOT1 p.Leu111fs Likely pathogenic ★ same condition
CNOT1 p.Ala1368Val Uncertain significance ★★ ⚠ same condition
CNOT1 p.His39Tyr Uncertain significance ★★ ⚠ same condition
CNOT1 c.1343+1G>T Pathogenic ★ same condition
CNOT1 p.Asp362Tyr Likely pathogenic ★ same condition
CNOT1 p.Gln1271Ter Likely pathogenic ★ same condition
CNOT1 p.Gln1740Ter Likely pathogenic ★ same condition
CNOT1 p.Gly918fs Likely pathogenic ★ 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-glu1268fs (accessed [today's date]).

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