MAP3K7 p.Pro512=
c.1536G>A · rs988683193 · VCV1992082
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00539%, 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 -3.6 |
| Overall | ||
| CADD | 8.932 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00539%
African / African-American · 4/74,160 alleles
Filtering AF
0.0022%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00195%
Overall
0.00259%
41/1,584,396 alleles · very rare
exomes 37/1,432,760 · genomes 4/151,636 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00539% | 18,540 |
| Admixed American | 0.00336% | 29,758 |
| European (non-Finnish) | 0.00303% | 32,997 |
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.Pro512=
- Coding
- c.1536G>A
- MANE Select
- NM_145331
- dbSNP
- rs988683193
- Type
- single nucleotide variant
- Location
- chr6:90518551 (GRCh38)
- Gene constraint
- LOEUF 0.397 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 70.27 · 25 PDB
- Residue 512
- a UniProt-annotated variant site (in fmd2; does not affect interaction with tab2; does not affect homodimerization; increases autophosphorylation; increases mapk signaling; increases nf-kappa-b signaling)
Similar variants
- MAP3K7 p.Pro512Leu Pathogenic ★★ same residue
- MAP3K7 p.Arg274Cys Pathogenic/Likely pathogenic ★★ same type
- MAP3K7 p.Gly110Ser Pathogenic/Likely 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
- MAP3K7 p.Arg347His 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-pro512 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown