Is TOE1 p.Arg345= (c.1035G>A) pathogenic?

TOE1 p.Arg345= (c.1035G>A) is classified Likely benign in TOE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-25). Ultra-rare (popmax 0.0659%, sas).

How common is TOE1 p.Arg345= (c.1035G>A) in the general population?

TOE1 p.Arg345= (c.1035G>A) is ultra-rare (popmax 0.0659%, sas) (gnomAD).

TOE1 p.Arg345=

c.1035G>A · rs553074656 · VCV2898823

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0659%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.38	GERP -3.5, phastCons 0.98
Overall
CADD	3.377	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0659% South Asian · 60/91,070 alleles

Filtering AF 0.0525% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0476%

Overall 0.00372% 60/1,614,022 alleles · ultra-rare exomes 56/1,461,852 · genomes 4/152,170 · joint denominator

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: TOE1
Protein: p.Arg345=
Coding: c.1035G>A
MANE Select: NM_025077
dbSNP: rs553074656
Type: single nucleotide variant
Location: chr1:45343204 (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

Similar variants

TOE1 p.Arg345Gln Uncertain significance ★ ⚠ same residue
TOE1 p.Arg345Pro Uncertain significance ★ ⚠ same residue
MUTYH p.Trp12Ter Pathogenic/Likely pathogenic ★★ same type
TOE1 p.Glu245Ter Pathogenic ★★ same type
MUTYH c.36+5G>A Uncertain significance ★★ same type
MUTYH p.Arg10His Uncertain significance ★★ ⚠ same type
MUTYH p.Arg7Leu Uncertain significance ★★ ⚠ same type
MUTYH p.Pro3Leu 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/toe1-p-arg345 (accessed [today's date]).

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