MAPKAPK3 p.Asp329=
c.987C>T · rs746823043 · VCV1934382
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0166%, 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 -0.12 | GERP -4.9, phastCons 0.74 |
| Overall | ||
| CADD | 7.803 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0166%
Middle Eastern · 1/6,034 alleles
Filtering AF
0.00139%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00117%
Overall
0.00189%
30/1,589,984 alleles · ultra-rare
exomes 30/1,437,670 · genomes 0/152,314 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0166% | 6,034 |
| African / African-American | 0.00402% | 24,882 |
| South Asian | 0.0023% | 43,513 |
| European (non-Finnish) | 0.00205% | 48,664 |
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.Asp329=
- Coding
- c.987C>T
- MANE Select
- NM_001243925
- dbSNP
- rs746823043
- Type
- single nucleotide variant
- Location
- chr3:50647194 (GRCh38)
- Gene constraint
- LOEUF 0.943 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.10 · 5 PDB
- Residue 329
- the 'autoinhibitory helix' region; an α-helix
Similar variants
- 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
- MAPKAPK3 p.Arg282His Uncertain significance ★★ ⚠ same type
- MAPKAPK3 p.Arg319Gln 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-asp329 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown