MAP2K1 p.Leu92=
c.276G>C · rs377323150 · VCV40783
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0133%, amr)
Conditions
1
RASopathy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.02 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.21 | GERP -3.8, phastCons 0.034 |
| Overall | ||
| CADD | 4.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0133%
Admixed American · 8/60,000 alleles
Filtering AF
0.00661%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00482%
Overall
0.000753%
11/1,461,518 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0133% | 7,500 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,500 |
| African / African-American | 0.00133% | 75,016 |
| South Asian | 0.0011% | 91,048 |
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
- MAP2K1
- Protein
- p.Leu92=
- Coding
- c.276G>C
- MANE Select
- NM_002755
- dbSNP
- rs377323150
- Type
- single nucleotide variant
- Location
- chr15:66435222 (GRCh38)
- Gene constraint
- LOEUF 0.515 · pLI 0.97 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 84.05 · 99 PDB
- Residue 92
- the protein kinase domain; a β-strand
Similar variants
- MAP2K1 p.Leu92Arg Pathogenic ★★★ same residue
- MAP2K1 p.Arg108Leu Likely pathogenic ★★★ same condition
- MAP2K1 p.Asn122Asp Pathogenic ★★★ ⚠ same condition
- MAP2K1 p.Asp67Asn Pathogenic ★★★ same condition
- MAP2K1 p.Glu203Gly Pathogenic ★★★ same condition
- MAP2K1 p.Leu42Arg Likely pathogenic ★★★ same condition
- MAP2K1 p.Leu42Phe Pathogenic ★★★ same condition
- MAP2K1 p.Lys57Gln Likely 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/map2k1-p-leu92 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown