MAP2K1 p.Phe223=
c.669C>T · rs1419207514 · VCV2852668
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00446%, eas)
Conditions
1
RASopathy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.097 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.29 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -2.3 | GERP -0.68 |
| Overall | ||
| CADD | 11.79 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,886 alleles
Filtering AF
0.000739%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000276%
Overall
0.000372%
6/1,614,056 alleles · very rare
exomes 4/1,461,736 · genomes 2/152,320 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00446% | 22,443 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,494 |
| South Asian | 0.0011% | 91,084 |
| European (non-Finnish) | 0.000169% | 589,974 |
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.Phe223=
- Coding
- c.669C>T
- MANE Select
- NM_002755
- dbSNP
- rs1419207514
- Type
- single nucleotide variant
- Location
- chr15:66481855 (GRCh38)
- Gene constraint
- LOEUF 0.515 · pLI 0.97 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 84.05 · 99 PDB
- Residue 223
- the protein kinase domain; an α-helix
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-phe223 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown