Is CNOT7 p.Lys124Arg (c.371A>G) pathogenic?

CNOT7 p.Lys124Arg (c.371A>G) is classified Uncertain significance in CNOT7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-25). AlphaMissense: likely benign (0.0882); Very rare (popmax 0.000169%, nfe).

How common is CNOT7 p.Lys124Arg (c.371A>G) in the general population?

CNOT7 p.Lys124Arg (c.371A>G) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about CNOT7 p.Lys124Arg (c.371A>G)?

AlphaMissense predicts likely benign (score 0.0882) — an in-silico prediction, not a clinical call.

CNOT7 p.Lys124Arg

c.371A>G · VCV3494506

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0882 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0882	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -7.82	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 7.9	GERP 2.8, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 11 kb · p 1.4e-11 · regional, not allelic
Overall
CADD	23.5	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 0.000169% European (non-Finnish) · 2/1,179,984 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,816 alleles · very rare

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: CNOT7
Protein: p.Lys124Arg
Coding: c.371A>G
MANE Select: NM_013354
Type: single nucleotide variant
Location: chr8:17237314 (GRCh38)
Gene constraint: LOEUF 0.255 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.28 · 5 PDB
Residue 124: an α-helix

Full CNOT7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

VPS37A c.-566G>A Benign ★★ same type
CNOT7 p.Arg186Gln Uncertain significance ★ ⚠ same type
CNOT7 p.Arg32Gln Uncertain significance ★ ⚠ same type
CNOT7 p.Asn19Ser Uncertain significance ★ ⚠ same type
CNOT7 p.Asn57Ser Uncertain significance ★ ⚠ same type
CNOT7 p.Asp7Tyr Uncertain significance ★ ⚠ same type
CNOT7 p.Gln210Glu Uncertain significance ★ ⚠ same type
CNOT7 p.Glu243Gly 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/cnot7-p-lys124arg (accessed [today's date]).

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