Is TBCK p.Ser697fs (c.2090_2091del) pathogenic?

TBCK p.Ser697fs (c.20902091del) is classified Likely pathogenic in TBCK (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-10). Associated with TBCK-related disorder.

What condition is associated with TBCK p.Ser697fs (c.2090_2091del)?

TBCK p.Ser697fs (c.2090_2091del) is associated with TBCK-related disorder (ClinVar).

TBCK p.Ser697fs

c.2090_2091del · VCV4968080

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

TBCK-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 23 of 26
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.9	GERP -0.76, phastCons 0.99

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

Variant & gene context

Gene: TBCK
Protein: p.Ser697fs
Coding: c.2090_2091del
MANE Select: NM_001163435
Type: Deletion
Location: chr4:106171239 (GRCh38)
Gene constraint: LOEUF 1.062 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.42

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

Disease context

TBCK-related disorder

Similar variants

TBCK p.Ser697Cys Uncertain significance ★ ⚠ same residue
TBCK p.Ser697Pro Uncertain significance ★ ⚠ same residue
TBCK c.2060-9del Likely benign same condition
TBCK c.1351-1G>A Likely pathogenic ★★ same condition
TBCK p.Lys455Ter Pathogenic ★★ same condition
TBCK p.Phe682fs Likely pathogenic ★★ same condition
TBCK p.Arg52Thr Uncertain significance ★★ same condition
TBCK p.Ile493fs 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/tbck-p-ser697fs (accessed [today's date]).

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