SYK p.Arg253=
c.759A>G · VCV4689070
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 4.39%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.25 | donor loss · deltas |
|---|---|---|
| Pangolin | Δ0.24 | loss · gain 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 5.1 | GERP -0.27, phastCons 1 |
| Overall | ||
| CADD | 11.01 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.39%
African / African-American · 3,296/75,022 alleles
Filtering AF
4.27%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.22%
Overall
0.231%
3,735/1,614,176 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.39% | 23 |
| Middle Eastern | 0.544% | 184 |
| Remaining individualsnot grpmax-eligible | 0.307% | 326 |
| Admixed American | 0.25% | 400 |
| South Asian | 0.00769% | 13,012 |
| European (non-Finnish) | 0.00483% | 20,702 |
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
- SYK
- Protein
- p.Arg253=
- Coding
- c.759A>G
- MANE Select
- NM_003177
- Type
- single nucleotide variant
- Location
- chr9:90864630 (GRCh38)
- Gene constraint
- LOEUF 0.302 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 84.52 · 93 PDB
- Residue 253
- the sh2 2 domain; a β-strand
Similar variants
- SYK p.Glu473Gln Uncertain significance ★★ ⚠ same type
- SYK c.1182-4G>A Benign ★★ same type
- SYK c.1182-7C>A Benign ★★ same type
- SYK c.1182-7C>G Benign ★★ same type
- SYK c.1582-16T>A Benign ★★ same type
- SYK c.796+20G>C Benign/Likely benign ★★ same type
- SYK p.Arg434= Benign ★★ same type
- SYK p.Asn499= 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/syk-p-arg253 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown