JAK1 p.Ser304=
c.912G>A · rs115098134 · VCV1169925
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.58%, 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 -16 | GERP -15 |
| Overall | ||
| CADD | 0.116 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.58%
African / African-American · 1,187/75,040 alleles
Filtering AF
1.51%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.48%
Overall
0.095%
1,533/1,614,166 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.58% | 63 |
| Admixed American | 0.145% | 690 |
| Remaining individualsnot grpmax-eligible | 0.131% | 762 |
| Middle Eastern | 0.066% | 1,516 |
| South Asian | 0.0384% | 2,602 |
| East Asian | 0.0223% | 4,489 |
| European (non-Finnish) | 0.0108% | 9,219 |
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
- JAK1
- Protein
- p.Ser304=
- Coding
- c.912G>A
- MANE Select
- NM_002227
- dbSNP
- rs115098134
- Type
- single nucleotide variant
- Location
- chr1:64866944 (GRCh38)
- Gene constraint
- LOEUF 0.168 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 85.68 · 52 PDB
- Residue 304
- the ferm domain
Similar variants
- JAK1 p.Ser304Leu Uncertain significance ★ ⚠ same residue
- JAK1 p.Arg1113Cys Uncertain significance ★★ ⚠ same type
- JAK1 p.Arg1113His Uncertain significance ★★ ⚠ same type
- JAK1 p.Arg219Gln Uncertain significance ★★ ⚠ same type
- JAK1 p.Arg360Trp Uncertain significance ★★ ⚠ same type
- JAK1 p.Arg454Trp Uncertain significance ★★ ⚠ same type
- JAK1 p.Arg49Trp Uncertain significance ★★ ⚠ same type
- JAK1 p.Arg514Cys 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/jak1-p-ser304 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown