MAPKAPK3 p.Pro252=
c.756G>A · rs936020820 · VCV1433803
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.23 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.16 | GERP -4.8, phastCons 0.37 |
| Overall | ||
| CADD | 15.78 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,058 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.000991%
16/1,614,076 alleles · ultra-rare
exomes 16/1,461,850 · genomes 0/152,226 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,058 |
| Admixed American | 0.005% | 20,003 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,251 |
| East Asian | 0.00223% | 44,872 |
| European (non-Finnish) | 0.000763% | 131,111 |
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
- MAPKAPK3
- Protein
- p.Pro252=
- Coding
- c.756G>A
- MANE Select
- NM_001243925
- dbSNP
- rs936020820
- Type
- single nucleotide variant
- Location
- chr3:50646191 (GRCh38)
- Gene constraint
- LOEUF 0.943 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.10 · 5 PDB
- Residue 252
- the protein kinase domain
Similar variants
- MAPKAPK3 p.Pro252Leu Uncertain significance ★★ ⚠ same residue
- MAPKAPK3 p.Pro252Ser Uncertain significance ★ ⚠ same residue
- MAPKAPK3 p.Ala181Ser Uncertain significance ★★ ⚠ same type
- MAPKAPK3 p.Arg112His Uncertain significance ★★ ⚠ same type
- MAPKAPK3 p.Arg148Gln Uncertain significance ★★ ⚠ same type
- MAPKAPK3 p.Arg148Trp Uncertain significance ★★ ⚠ same type
- MAPKAPK3 p.Arg259Cys Uncertain significance ★★ same type
- MAPKAPK3 p.Arg282Cys Uncertain significance ★★ ⚠ 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/mapkapk3-p-pro252 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown