MAP2K3 p.Leu166=
c.498T>C · rs529768181 · VCV742013
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.493%, sas)
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 -1.5 | GERP -5.1 |
| Overall | ||
| CADD | 4.338 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.493%
South Asian · 447/90,676 alleles
Filtering AF
0.455%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.44%
Overall
0.0299%
474/1,587,012 alleles · rare
exomes 449/1,435,256 · genomes 25/151,756 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.493% | 203 |
| Remaining individualsnot grpmax-eligible | 0.0378% | 2,643 |
| African / African-American | 0.0027% | 37,039 |
| Admixed American | 0.00169% | 59,104 |
| European (non-Finnish) | 8.6e-05% | 1,163,052 |
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.Leu166=
- Coding
- c.498T>C
- MANE Select
- NM_145109
- dbSNP
- rs529768181
- Type
- single nucleotide variant
- Location
- chr17:21302241 (GRCh38)
- Gene constraint
- LOEUF 0.993 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.13
- Residue 166
- 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-leu166 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown