Is CNOT3 p.Ser513fs (c.1538_1541del) pathogenic?

CNOT3 p.Ser513fs (c.15381541del) is classified Pathogenic in CNOT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-13). Associated with intellectual developmental disorder with speech delay, autism, and dysmorphic facies.

What condition is associated with CNOT3 p.Ser513fs (c.1538_1541del)?

CNOT3 p.Ser513fs (c.1538_1541del) is associated with intellectual developmental disorder with speech delay, autism, and dysmorphic facies (ClinVar).

CNOT3 p.Ser513fs

c.1538_1541del · VCV3600325

Pathogenic Single submitter

Classification

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 13 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.2	GERP 1.4, phastCons 1

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

Variant & gene context

Gene: CNOT3
Protein: p.Ser513fs
Coding: c.1538_1541del
MANE Select: NM_014516
Type: Deletion
Location: chr19:54149690 (GRCh38)
Gene constraint: LOEUF 0.057 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.53 · 6 PDB
Residue 513: 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.Ala376fs Pathogenic ★ same condition
CNOT3 p.Glu632fs Pathogenic ★ same condition
CNOT3 p.Gly493fs Pathogenic ★ same condition
CNOT3 p.Leu196fs Pathogenic ★ same condition
CNOT3 p.Lys682fs Pathogenic ★ same condition
CNOT3 p.Met189fs Pathogenic ★ same condition
CNOT3 p.Pro395fs Likely pathogenic ★ same condition
CNOT3 p.Pro537fs 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-ser513fs (accessed [today's date]).

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