TLK2 p.Ser595=
c.1785G>A · VCV4822472
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00271%, nfe)
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 0.63 | GERP 0.27, phastCons 1 |
| Overall | ||
| CADD | 13.68 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00271%
European (non-Finnish) · 32/1,179,794 alleles
Filtering AF
0.00196%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00168%
Overall
0.00211%
34/1,613,644 alleles · very rare
exomes 34/1,461,364 · genomes 0/152,280 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00271% | 36,869 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,464 |
| South Asian | 0.0011% | 91,054 |
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.Ser595=
- Coding
- c.1785G>A
- MANE Select
- NM_006852
- Type
- single nucleotide variant
- Location
- chr17:62602106 (GRCh38)
- Gene constraint
- LOEUF 0.103 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 73.15 · 2 PDB
- Residue 595
- the protein kinase domain; a UniProt-annotated variant site (in mrd57); a UniProt-annotated variant site (in mrd57; uncertain significance); an α-helix
Similar variants
- TLK2 p.Ser595Leu Pathogenic/Likely pathogenic ★★ same residue
- TLK2 p.Ser595Pro Likely pathogenic ★ same residue
- TLK2 p.Ser595Trp 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
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-ser595 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown