Is TOE1 p.Pro393Ser (c.1177C>T) pathogenic?

TOE1 p.Pro393Ser (c.1177C>T) is classified Uncertain significance in TOE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-17). AlphaMissense: likely benign (0.0665); Absent from gnomAD v4.1.

How common is TOE1 p.Pro393Ser (c.1177C>T) in the general population?

TOE1 p.Pro393Ser (c.1177C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TOE1 p.Pro393Ser (c.1177C>T)?

AlphaMissense predicts likely benign (score 0.0665) — an in-silico prediction, not a clinical call.

TOE1 p.Pro393Ser

c.1177C>T · VCV4742282

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0665 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0665	likely benign
REVEL	0.01	strongly benign-leaning
SaProt	LLR -5.41	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 -0.25	GERP -3.5
Regional constraint	o/e 0.83	unconstrained · MANE · 3,446 bp · p 1.6e-05 · regional, not allelic
Overall
CADD	0.937	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TOE1
Protein: p.Pro393Ser
Coding: c.1177C>T
MANE Select: NM_025077
Type: single nucleotide variant
Location: chr1:45343346 (GRCh38)
Gene constraint: LOEUF 1.225 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.16 · 1 PDB
Residue 393: a UniProt-annotated variant site (in pch7); the 'disordered' region

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

Similar variants

MUTYH p.Trp12Ter Pathogenic/Likely pathogenic ★★ same type
TOE1 p.Glu245Ter Pathogenic ★★ same type
MUTYH c.36+5G>A Uncertain significance ★★ same type
MUTYH p.Arg10His Uncertain significance ★★ ⚠ same type
MUTYH p.Arg7Leu Uncertain significance ★★ ⚠ same type
MUTYH p.Pro3Leu Uncertain significance ★★ ⚠ same type
TOE1 p.Arg184Cys Uncertain significance ★★ ⚠ same type
TOE1 p.Arg184His 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-pro393ser (accessed [today's date]).

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