Is CNOT1 p.Asp1772Glu (c.5316T>G) pathogenic?

CNOT1 p.Asp1772Glu (c.5316T>G) is classified Uncertain significance in CNOT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-26). AlphaMissense: likely benign (0.2216); Ultra-rare (popmax 0.0165%, mid); Associated with Vissers-Bodmer syndrome.

What condition is associated with CNOT1 p.Asp1772Glu (c.5316T>G)?

CNOT1 p.Asp1772Glu (c.5316T>G) is associated with Vissers-Bodmer syndrome (ClinVar).

How common is CNOT1 p.Asp1772Glu (c.5316T>G) in the general population?

CNOT1 p.Asp1772Glu (c.5316T>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CNOT1 p.Asp1772Glu (c.5316T>G)?

AlphaMissense predicts likely benign (score 0.2216) — an in-silico prediction, not a clinical call.

CNOT1 p.Asp1772Glu

c.5316T>G · rs2151911582 · VCV1285502

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2216 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Vissers-Bodmer syndrome

Computational evidence

Protein change
AlphaMissense	0.2216	likely benign
REVEL	0.194	benign-leaning
SaProt	LLR -3.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP -0.027, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 3,657 bp · p 4.4e-10 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Overall 0.000137% 2/1,461,856 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
European (non-Finnish)	8.47e-05%	1,180,043

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.Asp1772Glu
Coding: c.5316T>G
MANE Select: NM_016284
dbSNP: rs2151911582
Type: single nucleotide variant
Location: chr16:58537989 (GRCh38)
Gene constraint: LOEUF 0.064 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.22 · 21 PDB
Residue 1772: 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-asp1772glu (accessed [today's date]).

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