MAP2K2 p.Ala182=
c.546G>C · rs141402203 · VCV1083103
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00275%, nfe)
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 -20 | GERP -3.5 |
| Overall | ||
| CADD | 1.059 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00275%
European (non-Finnish) · 32/1,165,304 alleles
Filtering AF
0.00199%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0017%
Overall
0.00209%
33/1,582,534 alleles · very rare
exomes 30/1,430,734 · genomes 3/151,800 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00275% | 36,416 |
| African / African-American | 0.00135% | 74,240 |
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.Ala182=
- Coding
- c.546G>C
- MANE Select
- NM_030662
- dbSNP
- rs141402203
- Type
- single nucleotide variant
- Location
- chr19:4101263 (GRCh38)
- Gene constraint
- LOEUF 0.858 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.54 · 3 PDB
- Residue 182
- the protein kinase domain; an α-helix
Similar variants
- MAP2K2 p.Ala182Val 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
- MAP2K2 p.Arg231His Uncertain significance ★★★ ⚠ same condition
- MAP2K2 p.Arg231Leu Uncertain significance ★★★ ⚠ 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-ala182 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown