Is CNOT1 p.Glu871= (c.2613A>G) pathogenic?

CNOT1 p.Glu871= (c.2613A>G) is classified Benign/Likely benign in CNOT1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-31). Rare (popmax 0.222%, afr).

How common is CNOT1 p.Glu871= (c.2613A>G) in the general population?

CNOT1 p.Glu871= (c.2613A>G) is rare (popmax 0.222%, afr) (gnomAD).

CNOT1 p.Glu871=

c.2613A>G · rs148921058 · VCV2052173

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.222%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 1.4, phastCons 1
Overall
CADD	9.553	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.222% African / African-American · 166/74,774 alleles

Filtering AF 0.194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.184%

Overall 0.013% 210/1,610,988 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.222%	450
Middle Eastern	0.0335%	2,987
Remaining individualsnot grpmax-eligible	0.0305%	3,281
Admixed American	0.0202%	4,956
South Asian	0.00111%	90,446
European (non-Finnish)	0.000848%	117,905

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: CNOT1
Protein: p.Glu871=
Coding: c.2613A>G
MANE Select: NM_016284
dbSNP: rs148921058
Type: single nucleotide variant
Location: chr16:58555529 (GRCh38)
Gene constraint: LOEUF 0.064 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.22 · 21 PDB
Residue 871: an α-helix; the 'interaction with zfp36' region; a UniProt-annotated variant site (in vibos)

Full CNOT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNOT1 c.434-2A>G Pathogenic ★★ same type
CNOT1 p.Arg26Ter Pathogenic/Likely pathogenic ★★ same type
CNOT1 p.Arg535Cys Pathogenic ★★ ⚠ same type
CNOT1 c.310-3C>G Uncertain significance ★★ same type
CNOT1 c.5895+4T>C Uncertain significance ★★ same type
CNOT1 p.Ala1368Val Uncertain significance ★★ ⚠ same type
CNOT1 p.Ala1503Thr Uncertain significance ★★ ⚠ same type
CNOT1 p.Ala1604Gly 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/cnot1-p-glu871 (accessed [today's date]).

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