Is CNOT1 p.Arg1438Ter (c.4312C>T) pathogenic?

CNOT1 p.Arg1438Ter (c.4312C>T) is classified Uncertain significance in CNOT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-13). Absent from gnomAD v4.1; Associated with Vissers-Bodmer syndrome.

What condition is associated with CNOT1 p.Arg1438Ter (c.4312C>T)?

CNOT1 p.Arg1438Ter (c.4312C>T) is associated with Vissers-Bodmer syndrome (ClinVar).

How common is CNOT1 p.Arg1438Ter (c.4312C>T) in the general population?

CNOT1 p.Arg1438Ter (c.4312C>T) is absent from gnomAD v4.1 (gnomAD).

CNOT1 p.Arg1438Ter

c.4312C>T · rs2543899868 · VCV3234107

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Vissers-Bodmer syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 31 of 49
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP 0.36, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

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

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.Arg1438Ter
Coding: c.4312C>T
MANE Select: NM_016284
dbSNP: rs2543899868
Type: single nucleotide variant
Location: chr16:58543729 (GRCh38)
Gene constraint: LOEUF 0.064 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.22 · 21 PDB
Residue 1438: 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

Vissers-Bodmer syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CNOT1 p.Arg1438Leu Uncertain significance ★ ⚠ same residue
CNOT1 c.434-2A>G Pathogenic ★★ same condition
CNOT1 p.Arg26Ter Pathogenic/Likely pathogenic ★★ same condition
CNOT1 p.Arg535Cys Pathogenic ★★ same condition
CNOT1 c.310-3C>G Uncertain significance ★★ same condition
CNOT1 p.Leu1370Val Uncertain significance ★★ ⚠ same condition
CNOT1 p.Lys621Arg Uncertain significance ★★ ⚠ same condition
CNOT1 c.4006+12A>G Benign ★★ 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-arg1438ter (accessed [today's date]).

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