Is CNOT3 p.Arg697Ter (c.2089C>T) pathogenic?

CNOT3 p.Arg697Ter (c.2089C>T) is classified Pathogenic in CNOT3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-16). Absent from gnomAD v4.1; Associated with intellectual developmental disorder with speech delay, autism, and dysmorphic facies.

How common is CNOT3 p.Arg697Ter (c.2089C>T) in the general population?

CNOT3 p.Arg697Ter (c.2089C>T) is absent from gnomAD v4.1 (gnomAD).

CNOT3 p.Arg697Ter

Q: What condition is associated with CNOT3 p.Arg697Ter (c.2089C>T)?

CNOT3 p.Arg697Ter (c.2089C>T) is associated with intellectual developmental disorder with speech delay, autism, and dysmorphic facies (ClinVar).

c.2089C>T · rs2075273330 · VCV1707497

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

intellectual developmental disorder with speech delay, autism, and dysmorphic facies

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 17 of 18
REVEL	0.049	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 1, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CNOT3
Protein: p.Arg697Ter
Coding: c.2089C>T
MANE Select: NM_014516
dbSNP: rs2075273330
Type: single nucleotide variant
Location: chr19:54153766 (GRCh38)
Gene constraint: LOEUF 0.057 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.53 · 6 PDB
Residue 697: the 'repressor domain' region; a UniProt-annotated variant site (in iddsadf); a UniProt-annotated variant site (in iddsadf; uncertain significance); a β-strand

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

Disease context

intellectual developmental disorder with speech delay, autism, and dysmorphic facies — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CNOT3 p.Arg697Gln Uncertain significance ★ same residue
CNOT3 c.1904+2T>C Pathogenic/Likely pathogenic ★★ same condition
CNOT3 p.Arg81Ser Likely pathogenic ★★ same condition
CNOT3 p.Arg96Ter Pathogenic/Likely pathogenic ★★ same condition
CNOT3 p.Thr86= Likely pathogenic ★★ same condition
CNOT3 c.483+6T>G Uncertain significance ★★ same condition
CNOT3 p.Arg665His Uncertain significance ★★ ⚠ same condition
CNOT3 p.Gln453Leu 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-arg697ter (accessed [today's date]).

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