MAP3K2 p.Tyr422=
c.1266T>C · rs200753745 · VCV713753
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.271%, nfe)
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 1.2 | GERP -1, phastCons 0.99 |
| Overall | ||
| CADD | 6.869 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.271%
European (non-Finnish) · 3,171/1,170,260 alleles
Filtering AF
0.263%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.26%
Overall
0.211%
3,367/1,596,374 alleles · rare
exomes 3,149/1,444,024 · genomes 218/152,350 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.271% | 369 |
| Remaining individualsnot grpmax-eligible | 0.142% | 703 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0378% | 2,643 |
| Finnishnot grpmax-eligible | 0.0349% | 2,865 |
| South Asian | 0.034% | 2,943 |
| Middle Eastern | 0.0331% | 3,018 |
| Admixed American | 0.033% | 3,028 |
| African / African-American | 0.0321% | 3,119 |
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
- MAP3K2
- Protein
- p.Tyr422=
- Coding
- c.1266T>C
- MANE Select
- NM_001371910
- dbSNP
- rs200753745
- Type
- single nucleotide variant
- Location
- chr2:127317689 (GRCh38)
- Gene constraint
- LOEUF 0.6 · pLI 0.79 (gnomAD)
- Structure
- AlphaFold pLDDT 68.27 · 9 PDB
- Residue 422
- the protein kinase domain
Similar variants
- MAP3K2 p.Thr293= Benign ★★ same type
- MAP3K2 p.Ala178Val Uncertain significance ★ ⚠ same type
- MAP3K2 p.Ala487Thr Uncertain significance ★ ⚠ same type
- MAP3K2 p.Ala607Thr Uncertain significance ★ ⚠ same type
- MAP3K2 p.Arg151Trp Uncertain significance ★ ⚠ same type
- MAP3K2 p.Arg286Ile Uncertain significance ★ ⚠ same type
- MAP3K2 p.Arg328Lys Uncertain significance ★ ⚠ same type
- MAP3K2 p.Arg465His 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/map3k2-p-tyr422 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown