PTK2B p.Cys545=
c.1635C>T · VCV3940295
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0373%, 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 -2 | GERP -3.5 |
| Overall | ||
| CADD | 10.56 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0373%
African / African-American · 28/75,026 alleles
Filtering AF
0.0265%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0229%
Overall
0.0031%
50/1,610,548 alleles · ultra-rare
exomes 39/1,458,240 · genomes 11/152,308 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0373% | 2,679 |
| Middle Eastern | 0.033% | 3,028 |
| Remaining individualsnot grpmax-eligible | 0.00961% | 10,401 |
| South Asian | 0.00555% | 18,016 |
| Admixed American | 0.00168% | 59,528 |
| European (non-Finnish) | 0.000679% | 147,309 |
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
- PTK2B
- Protein
- p.Cys545=
- Coding
- c.1635C>T
- MANE Select
- NM_173176
- Type
- single nucleotide variant
- Location
- chr8:27437872 (GRCh38)
- Gene constraint
- LOEUF 0.562 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.47 · 26 PDB
- Residue 545
- the protein kinase domain
Similar variants
- PTK2B p.Gln359Glu Likely benign ★★ same type
- PTK2B p.Leu178= Benign ★★ same type
- PTK2B p.Pro413= Benign ★★ same type
- PTK2B p.Thr264Asn Likely benign ★★ same type
- PTK2B p.Ala258Thr Uncertain significance ★ ⚠ same type
- PTK2B p.Ala345Thr Uncertain significance ★ ⚠ same type
- PTK2B p.Ala709Val Uncertain significance ★ ⚠ same type
- PTK2B p.Ala799Val Uncertain significance ★ ⚠ 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/ptk2b-p-cys545 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown