TLK2 p.Lys704=
c.2112G>A · rs771204509 · VCV2648030
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0384%, sas)
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 3.3 | GERP 0.19, phastCons 1 |
| Overall | ||
| CADD | 7.588 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0384%
South Asian · 35/91,064 alleles
Filtering AF
0.0283%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0249%
Overall
0.00229%
37/1,613,902 alleles · ultra-rare
exomes 36/1,461,684 · genomes 1/152,218 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0384% | 2,602 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,239 |
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.Lys704=
- Coding
- c.2112G>A
- MANE Select
- NM_006852
- dbSNP
- rs771204509
- Type
- single nucleotide variant
- Location
- chr17:62612424 (GRCh38)
- Gene constraint
- LOEUF 0.103 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 73.15 · 2 PDB
- Residue 704
- the protein kinase domain; a UniProt-annotated variant site (in mrd57); a UniProt-annotated variant site (in mrd57; uncertain significance)
Similar variants
- TLK2 p.Lys704Arg Uncertain significance ★ same residue
- 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
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-lys704 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown