Is CNOT3 p.His179= (c.537C>T) pathogenic?

CNOT3 p.His179= (c.537C>T) is classified Likely benign in CNOT3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-01). Ultra-rare (popmax 0.0347%, afr); Associated with CNOT3-related disorder.

What condition is associated with CNOT3 p.His179= (c.537C>T)?

CNOT3 p.His179= (c.537C>T) is associated with CNOT3-related disorder (ClinVar).

How common is CNOT3 p.His179= (c.537C>T) in the general population?

CNOT3 p.His179= (c.537C>T) is ultra-rare (popmax 0.0347%, afr) (gnomAD).

CNOT3 p.His179=

c.537C>T · rs149814896 · VCV3042948

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0347%, afr)

Conditions

CNOT3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.142	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.7	GERP -3
Overall
CADD	7.294	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0347% African / African-American · 26/75,024 alleles

Filtering AF 0.0242% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0208%

Overall 0.0031% 50/1,613,792 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0347%	2,886
Middle Eastern	0.033%	3,031
Admixed American	0.0133%	7,502
South Asian	0.00329%	30,360
Remaining individualsnot grpmax-eligible	0.0032%	31,247
Finnishnot grpmax-eligible	0.00156%	63,978
European (non-Finnish)	0.000678%	147,468

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: CNOT3
Protein: p.His179=
Coding: c.537C>T
MANE Select: NM_014516
dbSNP: rs149814896
Type: single nucleotide variant
Location: chr19:54145651 (GRCh38)
Gene constraint: LOEUF 0.057 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.53 · 6 PDB
Residue 179: an α-helix

Full CNOT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CNOT3-related disorder

Similar variants

CNOT3 p.Glu710Lys Uncertain significance ★★ ⚠ same condition
CNOT3 c.703+1G>A Likely pathogenic ★ same condition
CNOT3 p.Arg57Gly Likely pathogenic ★ same condition
CNOT3 p.Gln61Ter Likely pathogenic ★ same condition
CNOT3 p.Gly406Ter Likely pathogenic ★ same condition
CNOT3 p.Tyr648Ter Likely pathogenic ★ same condition
CNOT3 p.Glu143Ala Uncertain significance ★ ⚠ same condition
CNOT3 p.Leu500Pro Uncertain significance ★ ⚠ 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/cnot3-p-his179 (accessed [today's date]).

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