Is TOE1 p.His319= (c.957C>T) pathogenic?

TOE1 p.His319= (c.957C>T) is classified Likely pathogenic in TOE1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-07-16). Very rare (popmax 0.00223%, eas); Associated with pontocerebellar hypoplasia type 7.

What condition is associated with TOE1 p.His319= (c.957C>T)?

TOE1 p.His319= (c.957C>T) is associated with pontocerebellar hypoplasia type 7 (ClinVar).

How common is TOE1 p.His319= (c.957C>T) in the general population?

TOE1 p.His319= (c.957C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

TOE1 p.His319=

c.957C>T · rs758153898 · VCV690334

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

pontocerebellar hypoplasia type 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4	GERP -3.5
Overall
CADD	3.913	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,866 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000479% 7/1,461,842 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,866
European (non-Finnish)	0.000508%	196,663

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.His319=
Coding: c.957C>T
MANE Select: NM_025077
dbSNP: rs758153898
Type: single nucleotide variant
Location: chr1:45343126 (GRCh38)
Gene constraint: LOEUF 1.225 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.16 · 1 PDB
Residue 319: a UniProt-annotated variant site (in pch7)

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.His319Gln Pathogenic same residue
TOE1 p.His319Tyr Likely pathogenic same residue
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
TOE1 p.Ile81Thr Uncertain significance ★★ ⚠ same condition
TOE1 c.237-2A>G 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-his319 (accessed [today's date]).

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