Is CNOT11 p.Pro287Ser (c.859C>T) pathogenic?

CNOT11 p.Pro287Ser (c.859C>T) is classified Uncertain significance in CNOT11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-09). AlphaMissense: likely pathogenic (0.9444); Absent from gnomAD v4.1.

How common is CNOT11 p.Pro287Ser (c.859C>T) in the general population?

CNOT11 p.Pro287Ser (c.859C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNOT11 p.Pro287Ser (c.859C>T)?

AlphaMissense predicts likely pathogenic (score 0.9444) — an in-silico prediction, not a clinical call.

CNOT11 p.Pro287Ser

c.859C>T · VCV4004371

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9444 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9444	likely pathogenic
REVEL	0.248	benign-leaning
SaProt	LLR -7.14	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 8,764 bp · p 0.022 · regional, not allelic
Overall
CADD	22.6	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: CNOT11
Protein: p.Pro287Ser
Coding: c.859C>T
MANE Select: NM_017546
Type: single nucleotide variant
Location: chr2:101264871 (GRCh38)
Gene constraint: LOEUF 0.583 · pLI 0.77 (gnomAD)
Structure: AlphaFold pLDDT 78.45 · 4 PDB
Residue 287: an α-helix

Full CNOT11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNOT11 p.Ala365Pro Uncertain significance ★ ⚠ same type
CNOT11 p.Arg202Cys Uncertain significance ★ ⚠ same type
CNOT11 p.Arg202His Uncertain significance ★ ⚠ same type
CNOT11 p.Arg286Cys Uncertain significance ★ ⚠ same type
CNOT11 p.Arg60Ser Uncertain significance ★ ⚠ same type
CNOT11 p.Asp307Glu Uncertain significance ★ ⚠ same type
CNOT11 p.Gln203His Uncertain significance ★ ⚠ same type
CNOT11 p.Gly36Ser 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/cnot11-p-pro287ser (accessed [today's date]).

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