JAK1 p.Arg877=
c.2629A>C · rs565648053 · VCV1593654
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.396%, 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 0.69 | GERP 1.4, phastCons 1 |
| Overall | ||
| CADD | 9.875 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.396%
Middle Eastern · 24/6,060 alleles
Filtering AF
0.273%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.232%
Overall
0.00923%
149/1,614,044 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.396% | 252 |
| South Asian | 0.0802% | 1,248 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,682 |
| Admixed American | 0.00833% | 12,005 |
| European (non-Finnish) | 0.0028% | 35,755 |
| African / African-American | 0.00266% | 37,526 |
| Finnishnot grpmax-eligible | 0.00156% | 64,032 |
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.Arg877=
- Coding
- c.2629A>C
- MANE Select
- NM_002227
- dbSNP
- rs565648053
- Type
- single nucleotide variant
- Location
- chr1:64841265 (GRCh38)
- Gene constraint
- LOEUF 0.168 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 85.68 · 52 PDB
- Residue 877
- a β-strand; the protein kinase 2 domain
Similar variants
- 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
- JAK1 p.Arg809Gln 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-arg877 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown