Is TOE1 p.Thr355fs (c.1062del) pathogenic?

TOE1 p.Thr355fs (c.1062del) is classified Likely pathogenic in TOE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-22). No gnomAD frequency available for this variant; Associated with pontocerebellar hypoplasia type 7.

What condition is associated with TOE1 p.Thr355fs (c.1062del)?

TOE1 p.Thr355fs (c.1062del) is associated with pontocerebellar hypoplasia type 7 (ClinVar).

How common is TOE1 p.Thr355fs (c.1062del) in the general population?

TOE1 p.Thr355fs (c.1062del) is no gnomAD frequency available for this variant (gnomAD).

TOE1 p.Thr355fs

c.1062del · rs2149260739 · VCV1687385

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

pontocerebellar hypoplasia type 7

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 0.79	GERP -1.5, phastCons 0.018

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TOE1
Protein: p.Thr355fs
Coding: c.1062del
MANE Select: NM_025077
dbSNP: rs2149260739
Type: Deletion
Location: chr1:45343228 (GRCh38)
Gene constraint: LOEUF 1.225 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.16 · 1 PDB
Residue 355: a UniProt-annotated variant site (in pch7); the 'disordered' region

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

Disease context

pontocerebellar hypoplasia type 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TOE1 p.Asn255fs Likely pathogenic ★ same condition
TOE1 p.Gln108fs Likely pathogenic ★ same condition
TOE1 p.Thr355Ser Uncertain significance ★ ⚠ same residue
TOE1 p.Gln314fs Pathogenic/Likely pathogenic ★★ same condition
TOE1 p.Arg253Trp Uncertain significance ★★ ⚠ same condition
TOE1 p.Asp387Asn Uncertain significance ★★ ⚠ same condition
TOE1 p.Gln314Glu Uncertain significance ★★ ⚠ same condition
TOE1 p.Gly480Asp Uncertain significance ★★ ⚠ 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-thr355fs (accessed [today's date]).

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