Is TOE1 p.Ile299= (c.897C>T) pathogenic?

TOE1 p.Ile299= (c.897C>T) is classified Benign/Likely benign in TOE1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-25). Rare (popmax 0.802%, afr).

How common is TOE1 p.Ile299= (c.897C>T) in the general population?

TOE1 p.Ile299= (c.897C>T) is rare (popmax 0.802%, afr) (gnomAD).

TOE1 p.Ile299=

c.897C>T · rs150174457 · VCV777907

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.802%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.1	GERP -2.5, phastCons 1
Overall
CADD	4.477	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.802% African / African-American · 601/74,916 alleles

Filtering AF 0.749% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.728%

Overall 0.048% 775/1,613,858 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.802%	125
Middle Eastern	0.165%	606
Remaining individualsnot grpmax-eligible	0.0944%	1,059
Admixed American	0.065%	1,538
European (non-Finnish)	0.00551%	18,153
South Asian	0.0011%	91,052

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.Ile299=
Coding: c.897C>T
MANE Select: NM_001048174 · reported on NM_025077
dbSNP: rs150174457
Type: single nucleotide variant
Location: chr1:45342987 (GRCh38)

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

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-ile299 (accessed [today's date]).

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