Is CNOT3 p.Lys31Ter (c.91A>T) pathogenic?

CNOT3 p.Lys31Ter (c.91A>T) is classified Pathogenic in CNOT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-13). Absent from gnomAD v4.1; Associated with intellectual developmental disorder with speech delay, autism, and dysmorphic facies.

How common is CNOT3 p.Lys31Ter (c.91A>T) in the general population?

CNOT3 p.Lys31Ter (c.91A>T) is absent from gnomAD v4.1 (gnomAD).

CNOT3 p.Lys31Ter

Q: What condition is associated with CNOT3 p.Lys31Ter (c.91A>T)?

CNOT3 p.Lys31Ter (c.91A>T) is associated with intellectual developmental disorder with speech delay, autism, and dysmorphic facies (ClinVar).

c.91A>T · VCV3387821

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 3 of 18
Splicing
SpliceAI	Δ0.88	donor gain · deltas
Pangolin	Δ0.81	gain · loss 0.64 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 1.2, phastCons 1
Overall
CADD	60.0	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.Lys31Ter
Coding: c.91A>T
MANE Select: NM_014516
Type: single nucleotide variant
Location: chr19:54143184 (GRCh38)
Gene constraint: LOEUF 0.057 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.53 · 6 PDB
Residue 31: an α-helix

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.Lys31= Likely pathogenic ★ 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.Thr86= Likely pathogenic ★★ same condition
CNOT3 c.483+6T>G Uncertain significance ★★ same condition
CNOT3 p.Arg665His 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-lys31ter (accessed [today's date]).

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