MAP2K2 p.Leu181=
c.543G>A · rs1218585349 · VCV2908350
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00231%, eas)
Conditions
1
RASopathy
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 5.9 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 12.41 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00231%
East Asian · 1/43,360 alleles
Overall
0.000126%
2/1,582,762 alleles · very rare
exomes 1/1,430,834 · genomes 1/151,928 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00231% | 43,360 |
| European (non-Finnish) | 8.58e-05% | 1,165,363 |
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
- MAP2K2
- Protein
- p.Leu181=
- Coding
- c.543G>A
- MANE Select
- NM_030662
- dbSNP
- rs1218585349
- Type
- single nucleotide variant
- Location
- chr19:4101266 (GRCh38)
- Gene constraint
- LOEUF 0.858 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.54 · 3 PDB
- Residue 181
- the protein kinase domain; an α-helix
Similar variants
- MAP2K2 p.Leu181Ser Uncertain significance ★★ ⚠ same residue
- MAP2K2 p.Leu181fs Uncertain significance ★ same residue
- MAP2K2 p.Leu181Met Uncertain significance ★ ⚠ same residue
- MAP2K2 p.Glu207Lys Likely pathogenic ★★★ same condition
- MAP2K2 p.Phe57Cys Pathogenic ★★★ same condition
- MAP2K2 p.Pro128Gln Pathogenic ★★★ same condition
- MAP2K2 p.Tyr134Cys Likely pathogenic ★★★ same condition
- MAP2K2 p.Tyr134His Pathogenic ★★★ same condition
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/map2k2-p-leu181 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown