PTK2 p.Ser355=
c.1065G>A · rs146407650 · VCV785269
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.62%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.076 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -13 | GERP -3.5 |
| Overall | ||
| CADD | 0.573 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.62%
African / African-American · 1,212/74,976 alleles
Filtering AF
1.54%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.51%
Overall
0.0868%
1,401/1,613,494 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.62% | 62 |
| Admixed American | 0.142% | 706 |
| Remaining individualsnot grpmax-eligible | 0.109% | 919 |
| East Asian | 0.00668% | 14,963 |
| European (non-Finnish) | 0.00254% | 39,318 |
| South Asian | 0.0022% | 45,531 |
| Finnishnot grpmax-eligible | 0.00156% | 64,014 |
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
- PTK2
- Protein
- p.Ser355=
- Coding
- c.1065G>A
- MANE Select
- NM_001352702
- dbSNP
- rs146407650
- Type
- single nucleotide variant
- Location
- chr8:140800487 (GRCh38)
- Gene constraint
- LOEUF 0.399 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 75.10 · 40 PDB
- Residue 355
- the ferm domain
Similar variants
- PTK2 p.Arg855Ter Uncertain significance ★★ same type
- PTK2 c.*705T>A Benign ★★ same type
- PTK2 p.Arg349= Benign ★★ same type
- PTK2 p.Asp703= Benign ★★ same type
- PTK2 p.Glu870= Benign/Likely benign ★★ same type
- PTK2 p.Pro690= Benign ★★ same type
- PTK2 p.Tyr969= Benign ★★ same type
- PTK2 p.Val215= Benign ★★ 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/ptk2-p-ser355 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown