MAPKAPK2 p.Thr66=
c.198C>T · rs140022471 · VCV729103
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.71%, afr)
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 2.5 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 14.46 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.71%
African / African-American · 501/70,612 alleles
Filtering AF
0.658%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.638%
Overall
0.0347%
538/1,548,420 alleles · rare
exomes 221/1,398,360 · genomes 317/150,060 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.71% | 141 |
| Remaining individualsnot grpmax-eligible | 0.0394% | 2,538 |
| Middle Eastern | 0.0348% | 2,876 |
| Admixed American | 0.0181% | 5,525 |
| European (non-Finnish) | 0.000175% | 571,461 |
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
- MAPKAPK2
- Protein
- p.Thr66=
- Coding
- c.198C>T
- MANE Select
- NM_032960
- dbSNP
- rs140022471
- Type
- single nucleotide variant
- Location
- chr1:206685427 (GRCh38)
- Gene constraint
- LOEUF 0.303 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 83.08 · 31 PDB
- Residue 66
- the protein kinase domain
Similar variants
- MAPKAPK2 p.Pro17= Likely benign ★★ same type
- MAPKAPK2 p.Ala111Val Uncertain significance ★ ⚠ same type
- MAPKAPK2 p.Ala33Gly Uncertain significance ★ ⚠ same type
- MAPKAPK2 p.Ala378Gly Uncertain significance ★ ⚠ same type
- MAPKAPK2 p.Ala390Thr Uncertain significance ★ ⚠ same type
- MAPKAPK2 p.Arg110Trp Uncertain significance ★ ⚠ same type
- MAPKAPK2 p.Arg119Gln Uncertain significance ★ ⚠ same type
- MAPKAPK2 p.Arg149Ter 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/mapkapk2-p-thr66 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown