Is CNOT3 p.Ser104Asn (c.311G>A) pathogenic?

CNOT3 p.Ser104Asn (c.311G>A) is classified Conflicting classifications of pathogenicity in CNOT3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-08-13). AlphaMissense: likely pathogenic (0.9998); Absent from gnomAD v4.1; Associated with intellectual developmental disorder with speech delay, autism, and dysmorphic facies.

How common is CNOT3 p.Ser104Asn (c.311G>A) in the general population?

CNOT3 p.Ser104Asn (c.311G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNOT3 p.Ser104Asn (c.311G>A)?

AlphaMissense predicts likely pathogenic (score 0.9998) — an in-silico prediction, not a clinical call.

CNOT3 p.Ser104Asn

Q: What condition is associated with CNOT3 p.Ser104Asn (c.311G>A)?

CNOT3 p.Ser104Asn (c.311G>A) is associated with intellectual developmental disorder with speech delay, autism, and dysmorphic facies (ClinVar).

c.311G>A · rs2517346791 · VCV2020778

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.9998	likely pathogenic · top 10% in CNOT3
REVEL	0.645	pathogenic-leaning
SaProt	LLR -12.48	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.17	constrained · MANE · 1,145 bp · p 1.7e-25 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Ser104Asn
Coding: c.311G>A
MANE Select: NM_014516
dbSNP: rs2517346791
Type: single nucleotide variant
Location: chr19:54144058 (GRCh38)
Gene constraint: LOEUF 0.057 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.53 · 6 PDB
Residue 104: a β-strand

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 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
CNOT3 p.Gln453Leu 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-ser104asn (accessed [today's date]).

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