MAPKAPK3 p.Ala338=
c.1014C>A · rs141140894 · VCV1141232
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0773%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.022 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.48 | GERP -4.7 |
| Overall | ||
| CADD | 5.554 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0773%
African / African-American · 58/75,020 alleles
Filtering AF
0.0613%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0556%
Overall
0.00731%
118/1,613,628 alleles · ultra-rare
exomes 88/1,461,302 · genomes 30/152,326 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0773% | 1,293 |
| Admixed American | 0.0334% | 2,998 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,926 |
| European (non-Finnish) | 0.00263% | 38,059 |
| South Asian | 0.0022% | 45,521 |
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.Ala338=
- Coding
- c.1014C>A
- MANE Select
- NM_001243925
- dbSNP
- rs141140894
- Type
- single nucleotide variant
- Location
- chr3:50647911 (GRCh38)
- Gene constraint
- LOEUF 0.943 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.10 · 5 PDB
- Residue 338
- the 'autoinhibitory helix' region; an α-helix
Similar variants
- MAPKAPK3 p.Ala338Thr Uncertain significance ★ ⚠ same residue
- MAPKAPK3 p.Ala338Val 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-ala338 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown