Is TOE1 p.Phe303del (c.908_910del) pathogenic?

TOE1 p.Phe303del (c.908910del) is classified Likely pathogenic in TOE1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-02-02). Very rare (popmax 0.0011%, sas); Associated with TOE1-related disorder.

What condition is associated with TOE1 p.Phe303del (c.908_910del)?

TOE1 p.Phe303del (c.908_910del) is associated with TOE1-related disorder (ClinVar).

How common is TOE1 p.Phe303del (c.908_910del) in the general population?

TOE1 p.Phe303del (c.908_910del) is very rare (popmax 0.0011%, sas) (gnomAD).

TOE1 p.Phe303del

c.908_910del · rs2524802526 · VCV2630730

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

TOE1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.4	GERP -0.49, phastCons 0.97

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,894 alleles

Overall 6.84e-05% 1/1,461,732 alleles · very rare

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.Phe303del
Coding: c.908_910del
MANE Select: NM_025077
dbSNP: rs2524802526
Type: Deletion
Location: chr1:45342996 (GRCh38)
Gene constraint: LOEUF 1.225 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.16 · 1 PDB
Residue 303: a UniProt-annotated variant site (in pch7); an α-helix

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

Disease context

TOE1-related disorder

Similar variants

TOE1 p.Gln314fs Pathogenic/Likely pathogenic ★★ same condition
TOE1 p.Asn255fs Likely pathogenic ★ same type
TOE1 p.Asn391fs Likely pathogenic ★ same type
TOE1 p.Gln108fs Likely pathogenic ★ same type
TOE1 p.Pro223fs Pathogenic ★ same type
TOE1 p.Thr355fs Likely pathogenic ★ same type
TOE1 c.334-5_334-3del Uncertain significance ★ same type
TOE1 p.Glu413_Ile414insTer 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-phe303del (accessed [today's date]).

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