Is CNOT3 p.Pro314fs (c.940_941delinsG) pathogenic?

CNOT3 p.Pro314fs (c.940941delinsG) is classified Likely pathogenic in CNOT3 (ClinVar, Single submitter, 1 submitter). Associated with intellectual developmental disorder with speech delay, autism, and dysmorphic facies.

What condition is associated with CNOT3 p.Pro314fs (c.940_941delinsG)?

CNOT3 p.Pro314fs (c.940_941delinsG) is associated with intellectual developmental disorder with speech delay, autism, and dysmorphic facies (ClinVar).

CNOT3 p.Pro314fs

c.940_941delinsG · VCV3767113

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 11 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.2	GERP -0.13, phastCons 0.98

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

Variant & gene context

Gene: CNOT3
Protein: p.Pro314fs
Coding: c.940_941delinsG
MANE Select: NM_014516
Type: Indel
Location: chr19:54148193 (GRCh38)
Gene constraint: LOEUF 0.057 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.53 · 6 PDB
Residue 314: the 'disordered' region

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.Ser245fs Pathogenic/Likely pathogenic ★★ same condition
CNOT3 p.Pro314Ser Benign ★★ same residue
CNOT3 c.1904+2T>C Pathogenic/Likely pathogenic ★★ same condition
CNOT3 p.Arg697Ter Pathogenic ★★ same condition
CNOT3 p.Arg81Ser Likely pathogenic ★★ same condition
CNOT3 p.Arg96Ter Pathogenic/Likely pathogenic ★★ same condition
CNOT3 p.Asn276fs Pathogenic ★★ same condition
CNOT3 p.Thr86= 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/cnot3-p-pro314fs (accessed [today's date]).

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