Is TOE1 p.Gln314fs (c.940_941del) pathogenic?

TOE1 p.Gln314fs (c.940941del) is classified Pathogenic/Likely pathogenic in TOE1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-10). Ultra-rare (popmax 0.0102%, nfe); Associated with TOE1-related disorder.

What condition is associated with TOE1 p.Gln314fs (c.940_941del)?

TOE1 p.Gln314fs (c.940_941del) is associated with TOE1-related disorder, pontocerebellar hypoplasia type 7 (ClinVar).

How common is TOE1 p.Gln314fs (c.940_941del) in the general population?

TOE1 p.Gln314fs (c.940_941del) is ultra-rare (popmax 0.0102%, nfe) (gnomAD).

TOE1 p.Gln314fs

c.940_941del · rs780563835 · VCV524117

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0102%, nfe)

Conditions

TOE1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (8 of 8) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP 0.57, phastCons 1
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0102% European (non-Finnish) · 120/1,179,788 alleles

Filtering AF 0.00867% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00812%

Overall 0.00787% 127/1,613,564 alleles · ultra-rare exomes 119/1,461,586 · genomes 8/151,978 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0102%	9,832
Remaining individualsnot grpmax-eligible	0.008%	12,493
African / African-American	0.00267%	37,406

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.Gln314fs
Coding: c.940_941del
MANE Select: NM_025077
dbSNP: rs780563835
Type: Microsatellite
Location: chr1:45343107 (GRCh38)
Gene constraint: LOEUF 1.225 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.16 · 1 PDB
Residue 314: 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

Also linked: pontocerebellar hypoplasia type 7

Similar variants

TOE1 p.Gln314Glu Uncertain significance ★★ ⚠ same residue
TOE1 p.Arg253Trp Uncertain significance ★★ ⚠ same condition
TOE1 p.Asp387Asn Uncertain significance ★★ ⚠ same condition
TOE1 p.Gly480Asp Uncertain significance ★★ ⚠ same condition
TOE1 p.Ile81Thr Uncertain significance ★★ ⚠ same condition
TOE1 c.237-2A>G Likely pathogenic ★ same condition
TOE1 c.913-2A>G Likely pathogenic ★ same condition
TOE1 p.Arg182Ter Likely pathogenic ★ 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-gln314fs (accessed [today's date]).

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