MAP2K1 p.Pro124=
c.372G>A · rs750270430 · VCV1548351
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
Conditions
2
Cardiovascular phenotype
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.127 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -15 | GERP -4.4 |
| Overall | ||
| CADD | 1.084 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/60,004 alleles
Filtering AF
0.00145%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00123%
Overall
0.00198%
32/1,614,144 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 30,002 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,254 |
| East Asian | 0.00223% | 44,884 |
| European (non-Finnish) | 0.00212% | 47,201 |
| African / African-American | 0.00133% | 75,042 |
| South Asian | 0.0011% | 91,080 |
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.Pro124=
- Coding
- c.372G>A
- MANE Select
- NM_002755
- dbSNP
- rs750270430
- Type
- single nucleotide variant
- Location
- chr15:66436826 (GRCh38)
- Gene constraint
- LOEUF 0.515 · pLI 0.97 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 84.05 · 99 PDB
- Residue 124
- the protein kinase domain
Similar variants
- MAP2K1 p.Pro124Ser Pathogenic ★★★ same residue
- MAP2K1 p.Pro124Leu Pathogenic/Likely pathogenic ★★ same residue
- MAP2K1 p.Pro124Ala Likely pathogenic ★ same residue
- MAP2K1 p.Pro124Arg Pathogenic ★ same residue
- MAP2K1 p.Pro124Thr Uncertain significance ★ ⚠ same residue
- MAP2K1 p.Pro124Gln Pathogenic same residue
- MAP2K1 p.Arg108Leu Likely pathogenic ★★★ same condition
- MAP2K1 p.Asn122Asp 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-pro124 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown