Is TLK2 p.Glu49fs (c.144del) pathogenic?

TLK2 p.Glu49fs (c.144del) is classified Pathogenic in TLK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-18). Associated with intellectual disability, autosomal dominant 57.

What condition is associated with TLK2 p.Glu49fs (c.144del)?

TLK2 p.Glu49fs (c.144del) is associated with intellectual disability, autosomal dominant 57 (ClinVar).

TLK2 p.Glu49fs

c.144del · VCV4857203

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 3 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.2	GERP 0.16, phastCons 1
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

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

Variant & gene context

Gene: TLK2
Protein: p.Glu49fs
Coding: c.144del
MANE Select: NM_006852
Type: Deletion
Location: chr17:62520833 (GRCh38)
Gene constraint: LOEUF 0.103 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.15 · 2 PDB
Residue 49: the 'disordered' region; 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 p.His486del Uncertain significance ★★ same condition
TLK2 c.1187_1188+18del Pathogenic ★ same condition
TLK2 p.Arg332fs Likely pathogenic ★ same condition
TLK2 p.Arg65fs Likely pathogenic ★ same condition
TLK2 p.Gln13fs Pathogenic ★ same condition
TLK2 p.Gln472fs Pathogenic ★ same condition
TLK2 p.Leu622fs Pathogenic ★ same condition
TLK2 p.Ser196fs 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/tlk2-p-glu49fs (accessed [today's date]).

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