MAP2K1 p.Ser212=
c.636C>T · rs138466751 · VCV138156
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0216%, nfe)
Conditions
2
Cardiovascular phenotype
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.172 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -9.6 | GERP -4.4 |
| Overall | ||
| CADD | 8.447 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0216%
European (non-Finnish) · 255/1,179,952 alleles
Filtering AF
0.0194%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0185%
Overall
0.0182%
294/1,613,784 alleles · ultra-rare
exomes 279/1,461,580 · genomes 15/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0216% | 4,627 |
| Remaining individualsnot grpmax-eligible | 0.0208% | 4,804 |
| African / African-American | 0.0174% | 5,764 |
| Admixed American | 0.0167% | 5,999 |
| East Asian | 0.00446% | 22,446 |
| Finnishnot grpmax-eligible | 0.00156% | 64,016 |
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.Ser212=
- Coding
- c.636C>T
- MANE Select
- NM_002755
- dbSNP
- rs138466751
- Type
- single nucleotide variant
- Location
- chr15:66481822 (GRCh38)
- Gene constraint
- LOEUF 0.515 · pLI 0.97 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 84.05 · 99 PDB
- Residue 212
- the protein kinase domain
Similar variants
- MAP2K1 p.Ser212Thr Likely 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.Leu92Arg 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-ser212 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown