MAP3K7 p.His129=
c.387C>T · rs368838835 · VCV2894123
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0823%, sas)
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 -4.7 | GERP -5.3 |
| Overall | ||
| CADD | 0.807 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0823%
South Asian · 75/91,090 alleles
Filtering AF
0.0673%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0617%
Overall
0.00564%
91/1,614,082 alleles · ultra-rare
exomes 86/1,461,882 · genomes 5/152,200 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0823% | 1,215 |
| East Asian | 0.00445% | 22,447 |
| Admixed American | 0.00167% | 60,014 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| European (non-Finnish) | 0.00102% | 98,337 |
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
- MAP3K7
- Protein
- p.His129=
- Coding
- c.387C>T
- MANE Select
- NM_145331
- dbSNP
- rs368838835
- Type
- single nucleotide variant
- Location
- chr6:90560171 (GRCh38)
- Gene constraint
- LOEUF 0.397 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 70.27 · 25 PDB
- Residue 129
- the protein kinase domain; the 'interaction with mapk8ip1' region; an α-helix
Similar variants
- MAP3K7 p.His129Gln Uncertain significance ★ ⚠ same residue
- MAP3K7 p.Arg274Cys Pathogenic/Likely pathogenic ★★ same type
- MAP3K7 p.Gly110Ser Pathogenic/Likely pathogenic ★★ same type
- MAP3K7 p.Pro512Leu Pathogenic ★★ same type
- MAP3K7 p.Ala313Thr Uncertain significance ★★ ⚠ same type
- MAP3K7 p.Ala400Thr Uncertain significance ★★ ⚠ same type
- MAP3K7 p.Ala6Thr Uncertain significance ★★ ⚠ same type
- MAP3K7 p.Arg289Gln 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/map3k7-p-his129 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown