PTK2 p.Pro774=
c.2322A>C · rs147531538 · VCV709439
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.238%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.086 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -14 | GERP -3.7 |
| Overall | ||
| CADD | 0.14 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.238%
European (non-Finnish) · 2,808/1,179,046 alleles
Filtering AF
0.231%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.228%
Overall
0.193%
3,106/1,613,092 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.238% | 420 |
| Remaining individualsnot grpmax-eligible | 0.191% | 525 |
| Admixed American | 0.17% | 588 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0878% | 1,139 |
| African / African-American | 0.0413% | 2,420 |
| Finnishnot grpmax-eligible | 0.0203% | 4,926 |
| South Asian | 0.00769% | 13,008 |
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.Pro774=
- Coding
- c.2322A>C
- MANE Select
- NM_001352702
- dbSNP
- rs147531538
- Type
- single nucleotide variant
- Location
- chr8:140706149 (GRCh38)
- Gene constraint
- LOEUF 0.399 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 75.10 · 40 PDB
- Residue 774
- the 'interaction with tgfb1i1' region
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.Ser355= Benign ★★ same type
- PTK2 p.Tyr969= 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-pro774 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown