Is CNOT6 p.Arg41Lys (c.122G>A) pathogenic?

CNOT6 p.Arg41Lys (c.122G>A) is classified Uncertain significance in CNOT6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-02). AlphaMissense: likely benign (0.1344); Absent from gnomAD v4.1.

How common is CNOT6 p.Arg41Lys (c.122G>A) in the general population?

CNOT6 p.Arg41Lys (c.122G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNOT6 p.Arg41Lys (c.122G>A)?

AlphaMissense predicts likely benign (score 0.1344) — an in-silico prediction, not a clinical call.

CNOT6 p.Arg41Lys

c.122G>A · rs2480583757 · VCV2331699

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1344 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1344	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -8.02	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 5.9	GERP 0.68, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 38 kb · p 5.7e-08 · regional, not allelic
Overall
CADD	21.7	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

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: CNOT6
Protein: p.Arg41Lys
Coding: c.122G>A
MANE Select: NM_001370472
dbSNP: rs2480583757
Type: single nucleotide variant
Location: chr5:180549940 (GRCh38)
Gene constraint: LOEUF 0.32 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.51 · 1 PDB

Full CNOT6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCR4 p.Ala246Thr Uncertain significance ★ ⚠ same type
CCR4 p.Ala246Val Uncertain significance ★ ⚠ same type
CCR4 p.Arg147Trp Uncertain significance ★ ⚠ same type
CCR4 p.Cys178Arg Uncertain significance ★ ⚠ same type
CCR4 p.Cys329Gly Uncertain significance ★ ⚠ same type
CCR4 p.Gln230Lys Uncertain significance ★ ⚠ same type
CCR4 p.His357Arg Uncertain significance ★ ⚠ same type
CCR4 p.Ile15Val Uncertain significance ★ ⚠ same type

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/cnot6-p-arg41lys (accessed [today's date]).

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