Is CNOT3 p.Ser415fs (c.1242dup) pathogenic?

CNOT3 p.Ser415fs (c.1242dup) is classified Pathogenic in CNOT3 (ClinVar, Single submitter, 1 submitter). Absent from gnomAD; Associated with intellectual developmental disorder with speech delay, autism, and dysmorphic facies.

How common is CNOT3 p.Ser415fs (c.1242dup) in the general population?

CNOT3 p.Ser415fs (c.1242dup) is absent from gnomAD (gnomAD).

CNOT3 p.Ser415fs

Q: What condition is associated with CNOT3 p.Ser415fs (c.1242dup)?

CNOT3 p.Ser415fs (c.1242dup) is associated with intellectual developmental disorder with speech delay, autism, and dysmorphic facies (ClinVar).

c.1242dup · rs2518137990 · VCV1707474

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

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

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
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

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.Ser415fs
Coding: c.1242dup
MANE Select: NM_014516
dbSNP: rs2518137990
Type: Duplication
Location: chr19:54148494 (GRCh38)
Gene constraint: LOEUF 0.057 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.53 · 6 PDB
Residue 415: 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.Ala480fs Likely pathogenic ★ same condition
CNOT3 p.Pro390fs Pathogenic ★ same condition
CNOT3 p.Ser459fs Pathogenic ★ same condition
CNOT3 p.Ser467fs Pathogenic ★ same condition
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

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-ser415fs (accessed [today's date]).

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