Is CNOT3 p.Lys31= (c.93G>A) pathogenic?

CNOT3 p.Lys31= (c.93G>A) is classified Likely pathogenic in CNOT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-29). Absent from gnomAD v4.1; Associated with intellectual developmental disorder with speech delay, autism, and dysmorphic facies.

How common is CNOT3 p.Lys31= (c.93G>A) in the general population?

CNOT3 p.Lys31= (c.93G>A) is absent from gnomAD v4.1 (gnomAD).

CNOT3 p.Lys31=

Q: What condition is associated with CNOT3 p.Lys31= (c.93G>A)?

CNOT3 p.Lys31= (c.93G>A) is associated with intellectual developmental disorder with speech delay, autism, and dysmorphic facies (ClinVar).

c.93G>A · rs2074521998 · VCV976757

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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.
Splicing
SpliceAI	Δ0.93	donor loss · deltas
Pangolin	Δ0.75	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.2, phastCons 1
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

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.Lys31=
Coding: c.93G>A
MANE Select: NM_014516
dbSNP: rs2074521998
Type: single nucleotide variant
Location: chr19:54143186 (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.Lys31Ter 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-lys31 (accessed [today's date]).

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