MAP2K3 p.Ser286=
c.858C>A · rs55736474 · VCV768857
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.643%, 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 -2.8 | GERP -5.1 |
| Overall | ||
| CADD | 4.087 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.643%
African / African-American · 477/74,170 alleles
Filtering AF
0.595%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.577%
Overall
0.0337%
540/1,603,474 alleles · rare
exomes 267/1,451,168 · genomes 273/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.643% | 155 |
| Admixed American | 0.0486% | 2,056 |
| Remaining individualsnot grpmax-eligible | 0.0419% | 2,385 |
| Middle Eastern | 0.0166% | 6,028 |
| South Asian | 0.00223% | 44,931 |
| European (non-Finnish) | 0.00051% | 196,048 |
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
- MAP2K3
- Protein
- p.Ser286=
- Coding
- c.858C>A
- MANE Select
- NM_145109
- dbSNP
- rs55736474
- Type
- single nucleotide variant
- Location
- chr17:21312225 (GRCh38)
- Gene constraint
- LOEUF 0.993 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.13
- Residue 286
- the protein kinase domain
Similar variants
- MAP2K3 p.Leu215Trp Uncertain significance ★★ ⚠ same type
- MAP2K3 c.568+10C>T Benign ★★ same type
- MAP2K3 p.Ala220= Benign ★★ same type
- MAP2K3 p.Ala225= Likely benign ★★ same type
- MAP2K3 p.Leu25= Benign ★★ same type
- MAP2K3 p.Leu319= Likely benign ★★ same type
- MAP2K3 p.Pro40Thr Benign ★★ same type
- MAP2K3 p.Thr39Ile Likely benign ★★ 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/map2k3-p-ser286 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown