Is TOE1 p.Ser11fs (c.31dup) pathogenic?

TOE1 p.Ser11fs (c.31dup) is classified Pathogenic in TOE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). Very rare (popmax 0.00667%, afr).

How common is TOE1 p.Ser11fs (c.31dup) in the general population?

TOE1 p.Ser11fs (c.31dup) is very rare (popmax 0.00667%, afr) (gnomAD).

TOE1 p.Ser11fs

c.31dup · VCV3690402

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.3	GERP 1.8, phastCons 0.6
Overall
CADD	27.8	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 0.00667% African / African-American · 5/74,938 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000372% 6/1,613,566 alleles · very rare exomes 4/1,461,324 · genomes 2/152,242 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,988
Remaining individualsnot grpmax-eligible	0.0016%	62,454

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.Ser11fs
Coding: c.31dup
MANE Select: NM_025077
Type: Duplication
Location: chr1:45340280 (GRCh38)

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

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-ser11fs (accessed [today's date]).

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