MAP2K2 p.Leu321=
c.963C>A · rs944839239 · VCV2040273
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, 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 0.004 | GERP -3.9, phastCons 0.79 |
| Overall | ||
| CADD | 1.734 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,814 alleles
Overall
6.2e-05%
1/1,612,968 alleles · very rare
exomes 1/1,460,876 · genomes 0/152,092 · joint denominator
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.Leu321=
- Coding
- c.963C>A
- MANE Select
- NM_030662
- dbSNP
- rs944839239
- Type
- single nucleotide variant
- Location
- chr19:4097300 (GRCh38)
- Gene constraint
- LOEUF 0.858 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.54 · 3 PDB
- Residue 321
- the protein kinase domain; an α-helix
Similar variants
- 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
- MAP2K2 p.Arg281Gln 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-leu321 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown