Is TOE1 p.Pro313Ala (c.937C>G) pathogenic?

TOE1 p.Pro313Ala (c.937C>G) is classified Likely pathogenic in TOE1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-07-16). AlphaMissense: likely benign (0.075); Very rare (popmax 8.48e-05%, nfe); Associated with pontocerebellar hypoplasia type 7.

What condition is associated with TOE1 p.Pro313Ala (c.937C>G)?

TOE1 p.Pro313Ala (c.937C>G) is associated with pontocerebellar hypoplasia type 7 (ClinVar).

How common is TOE1 p.Pro313Ala (c.937C>G) in the general population?

TOE1 p.Pro313Ala (c.937C>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about TOE1 p.Pro313Ala (c.937C>G)?

AlphaMissense predicts likely benign (score 0.075) — an in-silico prediction, not a clinical call.

TOE1 p.Pro313Ala

c.937C>G · rs1557531984 · VCV690333

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.075 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

pontocerebellar hypoplasia type 7

Computational evidence

Protein change
AlphaMissense	0.075	likely benign ⚠ discordant with ClinVar
REVEL	0.091	moderately benign-leaning
SaProt	LLR -6.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 0.57, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 3,446 bp · p 1.6e-05 · regional, not allelic
Overall
CADD	8.933	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,780 alleles

Overall 6.84e-05% 1/1,461,586 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.Pro313Ala
Coding: c.937C>G
MANE Select: NM_025077
dbSNP: rs1557531984
Type: single nucleotide variant
Location: chr1:45343106 (GRCh38)
Gene constraint: LOEUF 1.225 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.16 · 1 PDB
Residue 313: 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

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

Similar variants

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
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-pro313ala (accessed [today's date]).

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