Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.74%, 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 0.88 | GERP -2.3, phastCons 1 |
| Overall | ||
| CADD | 8.358 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.74%
African / African-American · 2,002/73,096 alleles
Filtering AF
2.64%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.6%
Overall
0.14%
2,207/1,580,522 alleles · low-frequency
exomes 1,124/1,428,290 · genomes 1,083/152,232 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.74% | 37 |
| Remaining individualsnot grpmax-eligible | 0.181% | 553 |
| Middle Eastern | 0.135% | 738 |
| Admixed American | 0.132% | 755 |
| European (non-Finnish) | 0.00129% | 77,738 |
| South Asian | 0.00117% | 85,474 |
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
- JAK2
- Protein
- p.Ser428=
- Coding
- c.1284T>C
- MANE Select
- NM_004972
- dbSNP
- rs2230727
- Type
- single nucleotide variant
- Location
- chr9:5066747 (GRCh38)
- Gene constraint
- LOEUF 0.848 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.46 · 171 PDB
- Residue 428
- the sh2; atypical domain
Similar variants
- JAK2 p.Arg133Trp Uncertain significance ★★ ⚠ same type
- JAK2 p.His587Asn Uncertain significance ★★ ⚠ same type
- JAK2 p.Ile899Val Uncertain significance ★★ ⚠ same type
- JAK2 p.Met32Val Uncertain significance ★★ ⚠ same type
- JAK2 p.Asn986= Benign ★★ same type
- JAK2 p.His163= Benign ★★ same type
- JAK2 c.1641+6T>C Conflicting classifications of pathogenicity ★ same type
- JAK2 p.Ala835Asp 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/jak2-p-ser428 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown