MAP2K1 p.Val369=
c.1107G>A · rs537811569 · VCV2893312
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0117%, amr)
Conditions
1
RASopathy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.26 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.12 | GERP -2.3, phastCons 0.091 |
| Overall | ||
| CADD | 11.37 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0117%
Admixed American · 7/60,026 alleles
Filtering AF
0.00543%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0038%
Overall
0.000558%
9/1,614,166 alleles · ultra-rare
exomes 5/1,461,848 · genomes 4/152,318 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0117% | 8,575 |
| European (non-Finnish) | 0.000169% | 590,005 |
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.Val369=
- Coding
- c.1107G>A
- MANE Select
- NM_002755
- dbSNP
- rs537811569
- Type
- single nucleotide variant
- Location
- chr15:66490540 (GRCh38)
- Gene constraint
- LOEUF 0.515 · pLI 0.97 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 84.05 · 99 PDB
Similar variants
- 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.Leu92Arg 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-val369 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown