Is CNOT10 p.Val151Met (c.451G>A) pathogenic?

CNOT10 p.Val151Met (c.451G>A) is classified Uncertain significance in CNOT10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-23). AlphaMissense: ambiguous (0.348); Very rare (popmax 0.00277%, afr).

How common is CNOT10 p.Val151Met (c.451G>A) in the general population?

CNOT10 p.Val151Met (c.451G>A) is very rare (popmax 0.00277%, afr) (gnomAD).

What do computational predictors say about CNOT10 p.Val151Met (c.451G>A)?

AlphaMissense predicts ambiguous (score 0.348) — an in-silico prediction, not a clinical call.

CNOT10 p.Val151Met

c.451G>A · rs1236971420 · VCV2549772

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.348 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00277%, afr)

Computational evidence

Protein change
AlphaMissense	0.348	ambiguous
REVEL	0.353	indeterminate
SaProt	LLR -10.57	damaging
Splicing
SpliceAI	Δ0.26	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 84 kb · p 3.3e-05 · regional, not allelic
Overall
CADD	32.0	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 0.00277% African / African-American · 2/72,204 alleles

Filtering AF 0.00046% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000172%

Overall 0.00019% 3/1,575,844 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00277%	36,102
European (non-Finnish)	8.55e-05%	1,169,926

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.Val151Met
Coding: c.451G>A
MANE Select: NM_015442
dbSNP: rs1236971420
Type: single nucleotide variant
Location: chr3:32713247 (GRCh38)
Gene constraint: LOEUF 0.405 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.87 · 2 PDB
Residue 151: an α-helix

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-val151met (accessed [today's date]).

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