Is TOE1 p.Arg341His (c.1022G>A) pathogenic?

TOE1 p.Arg341His (c.1022G>A) is classified Benign in TOE1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.1289); Low-frequency (popmax 3.91%, nfe).

How common is TOE1 p.Arg341His (c.1022G>A) in the general population?

TOE1 p.Arg341His (c.1022G>A) is low-frequency (popmax 3.91%, nfe) (gnomAD).

What do computational predictors say about TOE1 p.Arg341His (c.1022G>A)?

AlphaMissense predicts likely benign (score 0.1289) — an in-silico prediction, not a clinical call.

TOE1 p.Arg341His

c.1022G>A · rs9429157 · VCV1570041

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1289 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.91%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1289	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -7.77	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 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	22.7	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

Grpmax group 3.91% European (non-Finnish) · 46,195/1,179,986 alleles

Filtering AF 3.88% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.87%

Overall 3.25% 52,423/1,613,936 alleles · low-frequency exomes 49,005/1,461,840 · genomes 3,418/152,096 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	3.91%	26
Finnishnot grpmax-eligible	2.96%	34
Remaining individualsnot grpmax-eligible	2.48%	40
Ashkenazi Jewishnot grpmax-eligible	2.03%	49
Amishnot grpmax-eligible	1.43%	70
South Asian	1.12%	89
Admixed American	1.08%	92
African / African-American	0.618%	162
Middle Eastern	0.577%	173
East Asian	0.00223%	44,858

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.Arg341His
Coding: c.1022G>A
MANE Select: NM_025077
dbSNP: rs9429157
Type: single nucleotide variant
Location: chr1:45343191 (GRCh38)
Gene constraint: LOEUF 1.225 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.16 · 1 PDB
Residue 341: a UniProt-annotated variant site (in pch7); a UniProt-annotated variant site (in); the 'disordered' region

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

Similar variants

TOE1 p.Arg341Cys 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
TOE1 p.Arg184Cys 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-arg341his (accessed [today's date]).

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