Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.107%, 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 -20 | GERP -4.9 |
| Overall | ||
| CADD | 0.018 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.107%
African / African-American · 80/74,916 alleles
Filtering AF
0.0879%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0809%
Overall
0.0346%
557/1,610,292 alleles · rare
exomes 367/1,458,052 · genomes 190/152,240 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.107% | 936 |
| Middle Eastern | 0.0826% | 1,211 |
| Admixed American | 0.0434% | 2,306 |
| European (non-Finnish) | 0.0345% | 2,898 |
| Remaining individualsnot grpmax-eligible | 0.0289% | 3,464 |
| East Asian | 0.0156% | 6,412 |
| South Asian | 0.0121% | 8,266 |
| Finnishnot grpmax-eligible | 0.00625% | 16,007 |
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.Ser249=
- Coding
- c.747C>T
- MANE Select
- NM_145109
- dbSNP
- rs1657695
- Type
- single nucleotide variant
- Location
- chr17:21305101 (GRCh38)
- Gene constraint
- LOEUF 0.993 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.13
- Residue 249
- 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.Ser286= 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-ser249 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown