Is CNOT10 p.Phe316Val (c.946T>G) pathogenic?

CNOT10 p.Phe316Val (c.946T>G) is classified Uncertain significance in CNOT10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-30). AlphaMissense: likely pathogenic (0.8747); Absent from gnomAD v4.1.

How common is CNOT10 p.Phe316Val (c.946T>G) in the general population?

CNOT10 p.Phe316Val (c.946T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNOT10 p.Phe316Val (c.946T>G)?

AlphaMissense predicts likely pathogenic (score 0.8747) — an in-silico prediction, not a clinical call.

CNOT10 p.Phe316Val

c.946T>G · VCV4004368

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8747 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8747	likely pathogenic
REVEL	0.785	moderately pathogenic-leaning
SaProt	LLR -9.40	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 84 kb · p 3.3e-05 · regional, not allelic
Overall
CADD	28.0	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

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: CNOT10
Protein: p.Phe316Val
Coding: c.946T>G
MANE Select: NM_015442
Type: single nucleotide variant
Location: chr3:32725533 (GRCh38)
Gene constraint: LOEUF 0.405 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.87 · 2 PDB
Residue 316: 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-phe316val (accessed [today's date]).

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