Is CNOT2 p.Ter541= (c.*10_*23del) pathogenic?

CNOT2 p.Ter541= (c.1023del) is classified Conflicting classifications of pathogenicity in CNOT2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-04). Very rare (popmax 0.00226%, afr).

How common is CNOT2 p.Ter541= (c.*10_*23del) in the general population?

CNOT2 p.Ter541= (c.*10_*23del) is very rare (popmax 0.00226%, afr) (gnomAD).

CNOT2 p.Ter541=

c.*10_*23del · rs35192504 · VCV1686400

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00226%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function in a LoF-intolerant gene
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 0.44, phastCons 1
Overall
CADD	5.989	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	(A)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00226% African / African-American · 1/44,328 alleles

Filtering AF 0.000214% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00014%

Overall 0.000627% 8/1,275,472 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00226%	44,328
South Asian	0.0017%	58,854
European (non-Finnish)	0.000594%	168,270

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: CNOT2
Protein: p.Ter541=
Coding: c.*10_*23del
MANE Select: NM_014515
dbSNP: rs35192504
Type: Deletion
Location: chr12:70353914 (GRCh38)
Gene constraint: LOEUF 0.211 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 60.35 · 4 PDB

Full CNOT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNOT2 p.Ter541LeuextTer? Likely pathogenic ★ same residue
CNOT2 p.Gln457fs Likely pathogenic ★ same type
CNOT2 p.Tyr500fs 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/cnot2-p-ter541 (accessed [today's date]).

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