Is TOE1 p.Arg278Ser (c.834G>C) pathogenic?

TOE1 p.Arg278Ser (c.834G>C) is classified Uncertain significance in TOE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: likely benign (0.1257); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TOE1 p.Arg278Ser (c.834G>C)?

TOE1 p.Arg278Ser (c.834G>C) is associated with Inborn genetic diseases (ClinVar).

How common is TOE1 p.Arg278Ser (c.834G>C) in the general population?

TOE1 p.Arg278Ser (c.834G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TOE1 p.Arg278Ser (c.834G>C)?

AlphaMissense predicts likely benign (score 0.1257) — an in-silico prediction, not a clinical call.

TOE1 p.Arg278Ser

c.834G>C · VCV4188818

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1257 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1257	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -5.67	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 3,446 bp · p 1.6e-05 · regional, not allelic
Overall
CADD	13.64	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Arg278Ser
Coding: c.834G>C
MANE Select: NM_025077
Type: single nucleotide variant
Location: chr1:45342924 (GRCh38)
Gene constraint: LOEUF 1.225 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.16 · 1 PDB
Residue 278: a UniProt-annotated variant site (in pch7)

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.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
TOE1 p.Pro366Leu Uncertain significance ★★ ⚠ same condition
TOE1 p.Pro366Ser 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-arg278ser (accessed [today's date]).

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