MAP2K3 p.Ala291=
c.873C>T · rs56369732 · VCV768858
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0331%, mid)
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 -5 | GERP -5.1 |
| Overall | ||
| CADD | 2.415 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0331%
Middle Eastern · 2/6,050 alleles
Filtering AF
0.00687%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0053%
Overall
0.00256%
41/1,602,036 alleles · ultra-rare
exomes 36/1,449,858 · genomes 5/152,178 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0331% | 3,025 |
| South Asian | 0.0123% | 8,146 |
| Remaining individualsnot grpmax-eligible | 0.00323% | 30,973 |
| African / African-American | 0.00271% | 36,919 |
| European (non-Finnish) | 0.00204% | 49,002 |
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
- MAP2K3
- Protein
- p.Ala291=
- Coding
- c.873C>T
- MANE Select
- NM_145109
- dbSNP
- rs56369732
- Type
- single nucleotide variant
- Location
- chr17:21312240 (GRCh38)
- Gene constraint
- LOEUF 0.993 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.13
- Residue 291
- the protein kinase domain
Similar variants
- MAP2K3 p.Leu215Trp Uncertain significance ★★ ⚠ same type
- MAP2K3 c.568+10C>T Benign ★★ same type
- MAP2K3 p.Ala220= Benign ★★ same type
- MAP2K3 p.Ala225= Likely benign ★★ same type
- MAP2K3 p.Leu25= Benign ★★ same type
- MAP2K3 p.Leu319= Likely benign ★★ same type
- MAP2K3 p.Pro40Thr Benign ★★ same type
- MAP2K3 p.Ser286= Likely benign ★★ same type
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/map2k3-p-ala291 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown