JAK1 p.Ile432=
c.1296C>T · rs779970737 · VCV2067963
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00401%, 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 -4.2 | GERP -8 |
| Overall | ||
| CADD | 4.511 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00401%
African / African-American · 3/74,784 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000495%
Overall
0.000875%
14/1,599,244 alleles · very rare
exomes 13/1,447,086 · genomes 1/152,158 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00401% | 24,928 |
| Admixed American | 0.00336% | 29,730 |
| Remaining individualsnot grpmax-eligible | 0.00163% | 61,516 |
| South Asian | 0.00112% | 89,186 |
| European (non-Finnish) | 0.000598% | 167,163 |
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.Ile432=
- Coding
- c.1296C>T
- MANE Select
- NM_002227
- dbSNP
- rs779970737
- Type
- single nucleotide variant
- Location
- chr1:64860143 (GRCh38)
- Gene constraint
- LOEUF 0.168 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 85.68 · 52 PDB
- Residue 432
- an α-helix
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-ile432 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown