MAP2K2 p.Gly83=
c.249C>T · rs762268865 · VCV967817
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.01%, amr)
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 -3.6 | GERP -3.9 |
| Overall | ||
| CADD | 4.043 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.01%
Admixed American · 6/59,984 alleles
Filtering AF
0.00428%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00295%
Overall
0.00118%
19/1,613,586 alleles · ultra-rare
exomes 18/1,461,480 · genomes 1/152,106 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.01% | 9,997 |
| South Asian | 0.0011% | 91,086 |
| European (non-Finnish) | 0.00102% | 98,326 |
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.Gly83=
- Coding
- c.249C>T
- MANE Select
- NM_030662
- dbSNP
- rs762268865
- Type
- single nucleotide variant
- Location
- chr19:4117473 (GRCh38)
- Gene constraint
- LOEUF 0.858 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.54 · 3 PDB
- Residue 83
- the protein kinase domain; a binding site
Similar variants
- MAP2K2 p.Gly83Ser 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-gly83 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown