MAPKAPK5 p.Ala334=
c.1002G>A · VCV3905550
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.004%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -11 | GERP -3.8 |
| Overall | ||
| CADD | 1.263 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.004%
African / African-American · 3/75,030 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000494%
Overall
0.000929%
15/1,613,942 alleles · very rare
exomes 14/1,461,666 · genomes 1/152,276 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.004% | 25,010 |
| European (non-Finnish) | 0.00102% | 98,323 |
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
- MAPKAPK5
- Protein
- p.Ala334=
- Coding
- c.1002G>A
- MANE Select
- NM_003668
- Type
- single nucleotide variant
- Location
- chr12:111888520 (GRCh38)
- Gene constraint
- LOEUF 0.604 · pLI 0.28 (gnomAD)
- Structure
- AlphaFold pLDDT 78.84
Similar variants
- MAPKAPK5 p.Asn339Lys Uncertain significance ★★ ⚠ same type
- MAPKAPK5 p.Leu235= Likely benign ★★ same type
- MAPKAPK5 p.Ala10Thr Uncertain significance ★ ⚠ same type
- MAPKAPK5 p.Ala10Val Uncertain significance ★ ⚠ same type
- MAPKAPK5 p.Ala197Val Uncertain significance ★ ⚠ same type
- MAPKAPK5 p.Ala324Val Uncertain significance ★ ⚠ same type
- MAPKAPK5 p.Ala389Val Uncertain significance ★ ⚠ same type
- MAPKAPK5 p.Arg442Cys 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/mapkapk5-p-ala334 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown