Is TLK2 p.Met341fs (c.1021del) pathogenic?

TLK2 p.Met341fs (c.1021del) is classified Pathogenic in TLK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-02). Absent from gnomAD.

How common is TLK2 p.Met341fs (c.1021del) in the general population?

TLK2 p.Met341fs (c.1021del) is absent from gnomAD (gnomAD).

TLK2 p.Met341fs

c.1021del · rs1598676325 · VCV817367

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 12 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.9	GERP 1.9, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TLK2
Protein: p.Met341fs
Coding: c.1021del
MANE Select: NM_006852
dbSNP: rs1598676325
Type: Deletion
Location: chr17:62573264 (GRCh38)
Gene constraint: LOEUF 0.103 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.15 · 2 PDB
Residue 341: a UniProt-annotated variant site (in mrd57)

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

Similar variants

TLK2 p.Gln280fs Pathogenic ★★ same type
TLK2 p.His486del Uncertain significance ★★ same type
TLK2 c.1187_1188+18del Pathogenic ★ same type
TLK2 c.628-2_628del Likely pathogenic ★ same type
TLK2 p.Ala583fs Pathogenic ★ same type
TLK2 p.Arg240fs Likely pathogenic ★ same type
TLK2 p.Arg332fs Likely pathogenic ★ same type
TLK2 p.Arg65fs Likely pathogenic ★ 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/tlk2-p-met341fs (accessed [today's date]).

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