Is CNOT3 p.Pro458fs (c.1373del) pathogenic?

CNOT3 p.Pro458fs (c.1373del) is classified Pathogenic in CNOT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-01). Absent from gnomAD v4.1.

How common is CNOT3 p.Pro458fs (c.1373del) in the general population?

CNOT3 p.Pro458fs (c.1373del) is absent from gnomAD v4.1 (gnomAD).

CNOT3 p.Pro458fs

c.1373del · rs1213228037 · VCV1694942

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,611,782)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 12 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.2	GERP 1.2, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,611,782). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CNOT3
Protein: p.Pro458fs
Coding: c.1373del
MANE Select: NM_014516
dbSNP: rs1213228037
Type: Deletion
Location: chr19:54148705 (GRCh38)
Gene constraint: LOEUF 0.057 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.53 · 6 PDB
Residue 458: the 'disordered' region

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

Similar variants

CNOT3 p.Pro458Ala Uncertain significance ★★ ⚠ same residue
CNOT3 p.Pro458Ser Uncertain significance ★ ⚠ same residue
CNOT3 p.Ala376fs Pathogenic ★ same type
CNOT3 p.Ala475fs Likely pathogenic ★ same type
CNOT3 p.Glu632fs Pathogenic ★ same type
CNOT3 p.Gly493fs Pathogenic ★ same type
CNOT3 p.Leu196fs Pathogenic ★ same type
CNOT3 p.Lys682fs Pathogenic ★ 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/cnot3-p-pro458fs (accessed [today's date]).

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