TLK2 p.Ala694=
c.2082G>A · VCV3257051
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.476%, afr)
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 -11 | GERP -4.2 |
| Overall | ||
| CADD | 0.051 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.476%
African / African-American · 357/75,004 alleles
Filtering AF
0.435%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.419%
Overall
0.0311%
502/1,613,214 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.476% | 210 |
| South Asian | 0.0934% | 1,070 |
| Middle Eastern | 0.0826% | 1,211 |
| Remaining individualsnot grpmax-eligible | 0.0432% | 2,313 |
| Admixed American | 0.0234% | 4,280 |
| East Asian | 0.00223% | 44,856 |
| European (non-Finnish) | 0.0011% | 90,731 |
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.Ala694=
- Coding
- c.2082G>A
- MANE Select
- NM_006852
- Type
- single nucleotide variant
- Location
- chr17:62612394 (GRCh38)
- Gene constraint
- LOEUF 0.103 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 73.15 · 2 PDB
- Residue 694
- the protein kinase domain; a UniProt-annotated variant site (in mrd57); a UniProt-annotated variant site (in mrd57; uncertain significance); a turn
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-ala694 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown