Is CNOT1 p.Phe953= (c.2859C>T) pathogenic?

CNOT1 p.Phe953= (c.2859C>T) is classified Benign in CNOT1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-30). Common (popmax 15.1%, afr) — too common for a highly-penetrant pathogenic allele.

CNOT1 p.Phe953=

Q: How common is CNOT1 p.Phe953= (c.2859C>T) in the general population?

CNOT1 p.Phe953= (c.2859C>T) is common (popmax 15.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2859C>T · rs9941175 · VCV1289833

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 15.1%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.47	GERP -4.9
Overall
CADD	4.233	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 15.1% African / African-American · 11,313/74,970 alleles

Filtering AF 14.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.8%

Overall 0.923% 14,904/1,613,992 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	15.1%	7
Middle Eastern	3.48%	29
Remaining individualsnot grpmax-eligible	1.41%	71
Admixed American	1.18%	85
Ashkenazi Jewishnot grpmax-eligible	0.611%	164
European (non-Finnish)	0.128%	781
South Asian	0.104%	959
East Asian	0.00223%	44,878

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.Phe953=
Coding: c.2859C>T
MANE Select: NM_016284
dbSNP: rs9941175
Type: single nucleotide variant
Location: chr16:58555283 (GRCh38)
Gene constraint: LOEUF 0.064 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.22 · 21 PDB
Residue 953: 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-phe953 (accessed [today's date]).

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