Is TLK2 p.Trp620Ter (c.1860G>A) pathogenic?

TLK2 p.Trp620Ter (c.1860G>A) is classified Likely pathogenic in TLK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-09-04). Absent from gnomAD v4.1.

How common is TLK2 p.Trp620Ter (c.1860G>A) in the general population?

TLK2 p.Trp620Ter (c.1860G>A) is absent from gnomAD v4.1 (gnomAD).

TLK2 p.Trp620Ter

c.1860G>A · rs1568014839 · VCV620322

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,461,600)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 20 of 22
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Overall
CADD	49.0	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

No allele count reported in gnomAD v4.1 (AN 1,461,600). 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.Trp620Ter
Coding: c.1860G>A
MANE Select: NM_006852
dbSNP: rs1568014839
Type: single nucleotide variant
Location: chr17:62606130 (GRCh38)
Gene constraint: LOEUF 0.103 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.15 · 2 PDB
Residue 620: the protein kinase domain; a UniProt-annotated variant site (in mrd57); a UniProt-annotated variant site (in mrd57; uncertain significance)

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

Similar variants

TLK2 c.1121+1G>A Pathogenic/Likely pathogenic ★★ same type
TLK2 c.1550+1G>A Pathogenic/Likely pathogenic ★★ same type
TLK2 p.Arg11Ter Likely pathogenic ★★ same type
TLK2 p.Arg122Ter Pathogenic/Likely pathogenic ★★ same type
TLK2 p.Arg123Ter Pathogenic ★★ same type
TLK2 p.Arg262Ter Pathogenic ★★ same type
TLK2 p.Arg546Trp Pathogenic/Likely pathogenic ★★ same type
TLK2 p.Arg61Ter 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-trp620ter (accessed [today's date]).

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