Is TLK2 p.Ser289fs (c.865_866insTT) pathogenic?

TLK2 p.Ser289fs (c.865866insTT) is classified Pathogenic in TLK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-13). Associated with intellectual disability, autosomal dominant 57.

What condition is associated with TLK2 p.Ser289fs (c.865_866insTT)?

TLK2 p.Ser289fs (c.865_866insTT) is associated with intellectual disability, autosomal dominant 57 (ClinVar).

TLK2 p.Ser289fs

c.865_866insTT · VCV4528367

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

intellectual disability, autosomal dominant 57

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 11 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1

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

Variant & gene context

Gene: TLK2
Protein: p.Ser289fs
Coding: c.865_866insTT
MANE Select: NM_006852
Type: Insertion
Location: chr17:62565034 (GRCh38)
Gene constraint: LOEUF 0.103 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.15 · 2 PDB
Residue 289: a UniProt-annotated variant site (in mrd57)

Full TLK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability, autosomal dominant 57 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TLK2 c.1121+1G>A Pathogenic/Likely pathogenic ★★ same condition
TLK2 c.1550+1G>A Pathogenic/Likely pathogenic ★★ same condition
TLK2 p.Arg11Ter Likely pathogenic ★★ same condition
TLK2 p.Arg122Ter Pathogenic/Likely pathogenic ★★ same condition
TLK2 p.Arg123Ter Pathogenic ★★ same condition
TLK2 p.Arg262Ter Pathogenic ★★ same condition
TLK2 p.Arg546Trp Pathogenic/Likely pathogenic ★★ same condition
TLK2 p.Arg61Ter 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/tlk2-p-ser289fs (accessed [today's date]).

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