Is CNOT1 p.His54= (c.162T>C) pathogenic?

CNOT1 p.His54= (c.162T>C) is classified Likely benign in CNOT1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-20). Ultra-rare (popmax 0.092%, afr); Associated with CNOT1-related disorder.

What condition is associated with CNOT1 p.His54= (c.162T>C)?

CNOT1 p.His54= (c.162T>C) is associated with CNOT1-related disorder (ClinVar).

How common is CNOT1 p.His54= (c.162T>C) in the general population?

CNOT1 p.His54= (c.162T>C) is ultra-rare (popmax 0.092%, afr) (gnomAD).

CNOT1 p.His54=

c.162T>C · rs146964478 · VCV3053170

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.092%, afr)

Conditions

CNOT1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.50 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8	GERP 2.3, phastCons 1
Overall
CADD	12.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.092% African / African-American · 69/75,032 alleles

Filtering AF 0.0745% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0682%

Overall 0.00452% 73/1,614,006 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.092%	1,087
Remaining individualsnot grpmax-eligible	0.0048%	20,835
European (non-Finnish)	8.47e-05%	1,179,999

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.His54=
Coding: c.162T>C
MANE Select: NM_016284
dbSNP: rs146964478
Type: single nucleotide variant
Location: chr16:58588847 (GRCh38)
Gene constraint: LOEUF 0.064 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.22 · 21 PDB
Residue 54: a UniProt-annotated variant site (in vibos); an α-helix

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

Disease context

CNOT1-related disorder

Similar variants

CNOT1 p.Ala1368Val Uncertain significance ★★ ⚠ same condition
CNOT1 p.His39Tyr Uncertain significance ★★ ⚠ same condition
CNOT1 c.1343+1G>T Pathogenic ★ same condition
CNOT1 p.Asp362Tyr Likely pathogenic ★ same condition
CNOT1 p.Gln1271Ter Likely pathogenic ★ same condition
CNOT1 p.Gln1740Ter Likely pathogenic ★ same condition
CNOT1 p.Tyr2221Cys Likely pathogenic ★ same condition
CNOT1 p.Tyr424Ter Likely pathogenic ★ same condition

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-his54 (accessed [today's date]).

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