Is CNOT1 p.Arg38Trp (c.112C>T) pathogenic?

CNOT1 p.Arg38Trp (c.112C>T) is classified Uncertain significance in CNOT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-02). AlphaMissense: likely benign (0.2371); Very rare (popmax 0.00336%, amr).

How common is CNOT1 p.Arg38Trp (c.112C>T) in the general population?

CNOT1 p.Arg38Trp (c.112C>T) is very rare (popmax 0.00336%, amr) (gnomAD).

What do computational predictors say about CNOT1 p.Arg38Trp (c.112C>T)?

AlphaMissense predicts likely benign (score 0.2371) — an in-silico prediction, not a clinical call.

CNOT1 p.Arg38Trp

c.112C>T · rs774322576 · VCV1982843

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2371 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00336%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2371	likely benign
REVEL	0.209	benign-leaning
SaProt	LLR -10.88	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 43 kb · p 6e-23 · regional, not allelic
Overall
CADD	29.6	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

Grpmax group 0.00336% Admixed American · 2/59,600 alleles

Filtering AF 0.000557% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000745% 12/1,610,902 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00336%	29,800
European (non-Finnish)	0.000848%	117,893

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CNOT1
Protein: p.Arg38Trp
Coding: c.112C>T
MANE Select: NM_016284
dbSNP: rs774322576
Type: single nucleotide variant
Location: chr16:58588897 (GRCh38)
Gene constraint: LOEUF 0.064 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.22 · 21 PDB
Residue 38: a UniProt-annotated variant site (in vibos); an α-helix

Full CNOT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNOT1 c.434-2A>G Pathogenic ★★ same type
CNOT1 p.Arg26Ter Pathogenic/Likely pathogenic ★★ same type
CNOT1 p.Arg535Cys Pathogenic ★★ same type
CNOT1 c.310-3C>G Uncertain significance ★★ same type
CNOT1 c.5895+4T>C Uncertain significance ★★ same type
CNOT1 p.Ala1368Val Uncertain significance ★★ ⚠ same type
CNOT1 p.Ala1503Thr Uncertain significance ★★ ⚠ same type
CNOT1 p.Ala1604Gly Uncertain significance ★★ ⚠ same type

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/cnot1-p-arg38trp (accessed [today's date]).

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