Is CNOT10 p.Lys480Arg (c.1439A>G) pathogenic?

CNOT10 p.Lys480Arg (c.1439A>G) is classified Uncertain significance in CNOT10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-21). AlphaMissense: likely benign (0.0735); Ultra-rare (popmax 0.033%, mid).

How common is CNOT10 p.Lys480Arg (c.1439A>G) in the general population?

CNOT10 p.Lys480Arg (c.1439A>G) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about CNOT10 p.Lys480Arg (c.1439A>G)?

AlphaMissense predicts likely benign (score 0.0735) — an in-silico prediction, not a clinical call.

CNOT10 p.Lys480Arg

c.1439A>G · VCV4654960

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0735 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0735	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -7.94	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 11	GERP 2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 84 kb · p 3.3e-05 · regional, not allelic
Overall
CADD	23.9	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 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.00041% 6/1,461,848 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
European (non-Finnish)	0.000339%	295,004

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: CNOT10
Protein: p.Lys480Arg
Coding: c.1439A>G
MANE Select: NM_015442
Type: single nucleotide variant
Location: chr3:32734901 (GRCh38)
Gene constraint: LOEUF 0.405 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.87 · 2 PDB
Residue 480: the 'disordered' region

Full CNOT10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNOT10 p.Ala11Gly Uncertain significance ★ ⚠ same type
CNOT10 p.Ala225Val Uncertain significance ★ ⚠ same type
CNOT10 p.Ala250Val Uncertain significance ★ ⚠ same type
CNOT10 p.Ala279Thr Uncertain significance ★ ⚠ same type
CNOT10 p.Ala2Thr Uncertain significance ★ ⚠ same type
CNOT10 p.Ala305Val Uncertain significance ★ ⚠ same type
CNOT10 p.Ala319Ser Uncertain significance ★ ⚠ same type
CNOT10 p.Ala669Val 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/cnot10-p-lys480arg (accessed [today's date]).

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