SYK p.Ser54=
c.162C>T · VCV4848506
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 -20 | GERP -3.4 |
| Overall | ||
| CADD | 0.149 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,054 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00083%
Overall
0.00174%
28/1,612,434 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,054 |
| Remaining individualsnot grpmax-eligible | 0.00641% | 15,604 |
| African / African-American | 0.004% | 25,014 |
| European (non-Finnish) | 0.00161% | 62,059 |
| South Asian | 0.0011% | 90,786 |
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.Ser54=
- Coding
- c.162C>T
- MANE Select
- NM_003177
- Type
- single nucleotide variant
- Location
- chr9:90844060 (GRCh38)
- Gene constraint
- LOEUF 0.302 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 84.52 · 93 PDB
- Residue 54
- the sh2 1 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-ser54 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown