Is CNOT8 p.Ser282Arg (c.846C>G) pathogenic?

CNOT8 p.Ser282Arg (c.846C>G) is classified Uncertain significance in CNOT8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-08). AlphaMissense: ambiguous (0.4439); Absent from gnomAD v4.1.

How common is CNOT8 p.Ser282Arg (c.846C>G) in the general population?

CNOT8 p.Ser282Arg (c.846C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNOT8 p.Ser282Arg (c.846C>G)?

AlphaMissense predicts ambiguous (score 0.4439) — an in-silico prediction, not a clinical call.

CNOT8 p.Ser282Arg

c.846C>G · rs2481010384 · VCV3146640

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4439 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4439	ambiguous
REVEL	0.081	moderately benign-leaning
SaProt	LLR -6.81	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 2.1, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 59 bp · p 0.56 · regional, not allelic
Overall
CADD	22.2	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

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: CNOT8
Protein: p.Ser282Arg
Coding: c.846C>G
MANE Select: NM_001301073
dbSNP: rs2481010384
Type: single nucleotide variant
Location: chr5:154875406 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 90.51 · 1 PDB

Full CNOT8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNOT8 c.729+1G>T Uncertain significance ★ same type
CNOT8 p.Ala285Val Uncertain significance ★ ⚠ same type
CNOT8 p.Arg173Cys Uncertain significance ★ ⚠ same type
CNOT8 p.Asn289Ile Uncertain significance ★ ⚠ same type
CNOT8 p.Asp70Ala Uncertain significance ★ same type
CNOT8 p.Cys256Arg Uncertain significance ★ ⚠ same type
CNOT8 p.Gln219Glu Uncertain significance ★ ⚠ same type
CNOT8 p.Gln278Pro 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/cnot8-p-ser282arg (accessed [today's date]).

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