MAP3K7 p.Ile427=
c.1281C>T · rs1174061530 · VCV1664384
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00334%, amr)
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 12 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 14.82 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00334%
Admixed American · 2/59,844 alleles
Filtering AF
0.000554%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000429%
Overall
0.000868%
14/1,612,102 alleles · very rare
exomes 14/1,459,976 · genomes 0/152,126 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00334% | 29,922 |
| European (non-Finnish) | 0.00102% | 98,220 |
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.Ile427=
- Coding
- c.1281C>T
- MANE Select
- NM_145331
- dbSNP
- rs1174061530
- Type
- single nucleotide variant
- Location
- chr6:90544562 (GRCh38)
- Gene constraint
- LOEUF 0.397 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 70.27 · 25 PDB
Similar variants
- MAP3K7 p.Ile427Val 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-ile427 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown