Is TLK2 p.Lys487= (c.1461G>A) pathogenic?

TLK2 p.Lys487= (c.1461G>A) is classified Likely benign in TLK2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-06-22). Ultra-rare (popmax 0.0669%, mid); Associated with Inborn genetic diseases.

What condition is associated with TLK2 p.Lys487= (c.1461G>A)?

TLK2 p.Lys487= (c.1461G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TLK2 p.Lys487= (c.1461G>A) in the general population?

TLK2 p.Lys487= (c.1461G>A) is ultra-rare (popmax 0.0669%, mid) (gnomAD).

TLK2 p.Lys487=

c.1461G>A · rs374257770 · VCV1299863

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0669%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP -4.1, phastCons 1
Overall
CADD	15.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0669% Middle Eastern · 4/5,978 alleles

Filtering AF 0.0359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0312%

Overall 0.0144% 233/1,613,408 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0669%	1,495
Admixed American	0.05%	2,001
Remaining individualsnot grpmax-eligible	0.0224%	4,463
European (non-Finnish)	0.0147%	6,818
African / African-American	0.0147%	6,821
Finnishnot grpmax-eligible	0.00156%	64,022

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TLK2
Protein: p.Lys487=
Coding: c.1461G>A
MANE Select: NM_006852
dbSNP: rs374257770
Type: single nucleotide variant
Location: chr17:62596585 (GRCh38)
Gene constraint: LOEUF 0.103 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.15 · 2 PDB
Residue 487: the protein kinase domain; a UniProt-annotated variant site (in mrd57); a UniProt-annotated variant site (in mrd57; uncertain significance); a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TLK2 p.Arg546Trp Pathogenic/Likely pathogenic ★★ same condition
TLK2 p.Arg724Gln Uncertain significance ★★ ⚠ same condition
TLK2 p.Thr98Ala Uncertain significance ★★ ⚠ same condition
TLK2 p.Tyr129Cys Uncertain significance ★★ ⚠ same condition
TLK2 c.1189-2A>G Pathogenic ★ same condition
TLK2 p.Trp643Ter Pathogenic ★ same condition
TLK2 c.1971+2T>C Uncertain significance ★ same condition
TLK2 p.Ala135Pro Uncertain significance ★ ⚠ 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-lys487 (accessed [today's date]).

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