Is TOE1 p.Arg345Pro (c.1034G>C) pathogenic?

TOE1 p.Arg345Pro (c.1034G>C) is classified Uncertain significance in TOE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-24). AlphaMissense: ambiguous (0.4108); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TOE1 p.Arg345Pro (c.1034G>C)?

TOE1 p.Arg345Pro (c.1034G>C) is associated with Inborn genetic diseases (ClinVar).

How common is TOE1 p.Arg345Pro (c.1034G>C) in the general population?

TOE1 p.Arg345Pro (c.1034G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TOE1 p.Arg345Pro (c.1034G>C)?

AlphaMissense predicts ambiguous (score 0.4108) — an in-silico prediction, not a clinical call.

TOE1 p.Arg345Pro

c.1034G>C · VCV3809433

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4108 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4108	ambiguous
REVEL	0.138	moderately benign-leaning
SaProt	LLR -14.75	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 0.83, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 3,446 bp · p 1.6e-05 · regional, not allelic
Overall
CADD	23.2	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: TOE1
Protein: p.Arg345Pro
Coding: c.1034G>C
MANE Select: NM_025077
Type: single nucleotide variant
Location: chr1:45343203 (GRCh38)
Gene constraint: LOEUF 1.225 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.16 · 1 PDB
Residue 345: a UniProt-annotated variant site (in pch7); the 'disordered' region

Full TOE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TOE1 p.Arg345Gln Uncertain significance ★ ⚠ same residue
TOE1 p.Arg345= Likely benign ★ same residue
TOE1 p.Arg184Cys Uncertain significance ★★ ⚠ same condition
TOE1 p.Arg184His Uncertain significance ★★ ⚠ same condition
TOE1 p.Arg185Gln Uncertain significance ★★ ⚠ same condition
TOE1 p.Arg253Trp Uncertain significance ★★ ⚠ same condition
TOE1 p.Arg293His Uncertain significance ★★ ⚠ same condition
TOE1 p.Arg494His 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/toe1-p-arg345pro (accessed [today's date]).

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