Is CNOT3 p.Val660fs (c.1979_1980del) pathogenic?

CNOT3 p.Val660fs (c.19791980del) is classified Pathogenic in CNOT3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-27). Absent from gnomAD.

How common is CNOT3 p.Val660fs (c.1979_1980del) in the general population?

CNOT3 p.Val660fs (c.1979_1980del) is absent from gnomAD (gnomAD).

CNOT3 p.Val660fs

c.1979_1980del · rs2075208108 · VCV916115

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 16 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.4	GERP 1, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Val660fs
Coding: c.1979_1980del
MANE Select: NM_014516
dbSNP: rs2075208108
Type: Microsatellite
Location: chr19:54152939 (GRCh38)
Gene constraint: LOEUF 0.057 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.53 · 6 PDB
Residue 660: a UniProt-annotated variant site (in iddsadf); an α-helix

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

Similar variants

CNOT3 p.Asn276fs Pathogenic ★★ same type
CNOT3 p.Asp630_Ser631insTer Pathogenic ★ same type
CNOT3 p.Ile571del Likely pathogenic ★ same type
CNOT3 p.Lys50del Likely pathogenic ★ same type
CNOT3 p.245SH[3] Uncertain significance ★ same type
CNOT3 p.Asp285del Uncertain significance ★ same type
CNOT3 p.Gly402_Ser403insGlyGly Conflicting classifications of pathogenicity ★ same type
CNOT3 p.Lys737del 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/cnot3-p-val660fs (accessed [today's date]).

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