MAP2K2 p.Ala355=
c.1065G>A · rs374807671 · VCV46227
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0166%, mid)
Conditions
2
Cardiovascular phenotype
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -11 | GERP -3.5 |
| Overall | ||
| CADD | 0.827 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0166%
Middle Eastern · 1/6,012 alleles
Filtering AF
0.00749%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00549%
Overall
0.00217%
34/1,569,216 alleles · ultra-rare
exomes 28/1,416,894 · genomes 6/152,322 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0166% | 6,012 |
| Admixed American | 0.0152% | 6,598 |
| African / African-American | 0.00941% | 10,627 |
| Remaining individualsnot grpmax-eligible | 0.00658% | 15,197 |
| East Asian | 0.00232% | 43,072 |
| South Asian | 0.00117% | 85,394 |
| European (non-Finnish) | 0.00104% | 96,368 |
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
- MAP2K2
- Protein
- p.Ala355=
- Coding
- c.1065G>A
- MANE Select
- NM_030662
- dbSNP
- rs374807671
- Type
- single nucleotide variant
- Location
- chr19:4094480 (GRCh38)
- Gene constraint
- LOEUF 0.858 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.54 · 3 PDB
- Residue 355
- the protein kinase domain; a turn
Similar variants
- MAP2K2 p.Ala355Pro Uncertain significance ★★ ⚠ same residue
- MAP2K2 p.Ala355Val Uncertain significance ★★ ⚠ same residue
- MAP2K2 p.Glu207Lys Likely pathogenic ★★★ same condition
- MAP2K2 p.Phe57Cys Pathogenic ★★★ same condition
- MAP2K2 p.Pro128Gln Pathogenic ★★★ same condition
- MAP2K2 p.Tyr134Cys Likely pathogenic ★★★ same condition
- MAP2K2 p.Tyr134His Pathogenic ★★★ same condition
- MAP2K2 p.Arg231His Uncertain significance ★★★ ⚠ 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/map2k2-p-ala355 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown