MAP3K7 p.Thr224=
c.672G>A · rs545383999 · VCV2185110
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.011%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.2 | GERP -5.6 |
| Overall | ||
| CADD | 6.584 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.011%
South Asian · 10/91,068 alleles
Filtering AF
0.00594%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00533%
Overall
0.00626%
101/1,613,754 alleles · ultra-rare
exomes 93/1,461,714 · genomes 8/152,040 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.011% | 9,107 |
| European (non-Finnish) | 0.00703% | 14,215 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,624 |
| African / African-American | 0.00534% | 18,738 |
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.Thr224=
- Coding
- c.672G>A
- MANE Select
- NM_145331
- dbSNP
- rs545383999
- Type
- single nucleotide variant
- Location
- chr6:90553522 (GRCh38)
- Gene constraint
- LOEUF 0.397 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 70.27 · 25 PDB
- Residue 224
- the protein kinase domain; the 'interaction with mapk8ip1' region; an α-helix
Similar variants
- MAP3K7 p.Thr224Met Likely benign ★ ⚠ 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-thr224 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown