Is CNOT1 p.Asn761Ser (c.2282A>G) pathogenic?

CNOT1 p.Asn761Ser (c.2282A>G) is classified Conflicting classifications of pathogenicity in CNOT1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-01-23). AlphaMissense: likely benign (0.056); Ultra-rare (popmax 0.033%, sas); Associated with Inborn genetic diseases.

What condition is associated with CNOT1 p.Asn761Ser (c.2282A>G)?

CNOT1 p.Asn761Ser (c.2282A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CNOT1 p.Asn761Ser (c.2282A>G) in the general population?

CNOT1 p.Asn761Ser (c.2282A>G) is ultra-rare (popmax 0.033%, sas) (gnomAD).

What do computational predictors say about CNOT1 p.Asn761Ser (c.2282A>G)?

AlphaMissense predicts likely benign (score 0.056) — an in-silico prediction, not a clinical call.

CNOT1 p.Asn761Ser

c.2282A>G · rs754113666 · VCV1976998

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.056 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.056	likely benign
REVEL	0.189	benign-leaning
SaProt	LLR -5.03	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 5	GERP 1.2, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 43 kb · p 6e-23 · regional, not allelic
Overall
CADD	23.3	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 0.033% South Asian · 30/90,998 alleles

Filtering AF 0.0237% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0205%

Overall 0.0102% 164/1,613,458 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.033%	3,033
Admixed American	0.0167%	5,993
Middle Eastern	0.0165%	6,056
Finnishnot grpmax-eligible	0.0141%	7,109
European (non-Finnish)	0.00882%	11,344
East Asian	0.00669%	14,943
Remaining individualsnot grpmax-eligible	0.0064%	15,618
African / African-American	0.004%	24,973

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.Asn761Ser
Coding: c.2282A>G
MANE Select: NM_016284
dbSNP: rs754113666
Type: single nucleotide variant
Location: chr16:58558523 (GRCh38)
Gene constraint: LOEUF 0.064 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.22 · 21 PDB
Residue 761: the 'disordered' region; 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-asn761ser (accessed [today's date]).

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