Is CNOT1 p.Arg900Cys (c.2698C>T) pathogenic?

CNOT1 p.Arg900Cys (c.2698C>T) is classified Pathogenic in CNOT1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-09-29). AlphaMissense: likely pathogenic (0.9449); Very rare (popmax 8.47e-05%, nfe); Associated with Vissers-Bodmer syndrome.

What condition is associated with CNOT1 p.Arg900Cys (c.2698C>T)?

CNOT1 p.Arg900Cys (c.2698C>T) is associated with Vissers-Bodmer syndrome (ClinVar).

How common is CNOT1 p.Arg900Cys (c.2698C>T) in the general population?

CNOT1 p.Arg900Cys (c.2698C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CNOT1 p.Arg900Cys (c.2698C>T)?

AlphaMissense predicts likely pathogenic (score 0.9449) — an in-silico prediction, not a clinical call.

CNOT1 p.Arg900Cys

c.2698C>T · rs2040599000 · VCV978823

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9449 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Vissers-Bodmer syndrome

Computational evidence

Protein change
AlphaMissense	0.9449	likely pathogenic ✓ concordant with ClinVar
REVEL	0.402	indeterminate
SaProt	LLR -13.38	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.21	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 9.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.40	unconstrained · MANE · 2,090 bp · p 3.9e-16 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,000 alleles

Overall 6.2e-05% 1/1,614,058 alleles · very rare exomes 1/1,461,820 · genomes 0/152,238 · joint denominator

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: CNOT1
Protein: p.Arg900Cys
Coding: c.2698C>T
MANE Select: NM_016284
dbSNP: rs2040599000
Type: single nucleotide variant
Location: chr16:58555444 (GRCh38)
Gene constraint: LOEUF 0.064 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.22 · 21 PDB
Residue 900: an α-helix; the 'interaction with zfp36' region; a UniProt-annotated variant site (in vibos)

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 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
CNOT1 c.5896-5C>T 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-arg900cys (accessed [today's date]).

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