MAPK3 p.Ala109=
c.327G>A · rs151100121 · VCV726200
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0796%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.016 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -4.6 | GERP -3.6 |
| Overall | ||
| CADD | 6.018 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0796%
European (non-Finnish) · 939/1,180,020 alleles
Filtering AF
0.0753%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0736%
Overall
0.0623%
1,006/1,613,928 alleles · ultra-rare
exomes 943/1,461,730 · genomes 63/152,198 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0796% | 1,257 |
| Finnishnot grpmax-eligible | 0.0391% | 2,557 |
| Remaining individualsnot grpmax-eligible | 0.0272% | 3,675 |
| African / African-American | 0.0133% | 7,493 |
| Admixed American | 0.01% | 9,997 |
| South Asian | 0.00878% | 11,386 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,604 |
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
- MAPK3
- Protein
- p.Ala109=
- Coding
- c.327G>A
- MANE Select
- NM_002746
- dbSNP
- rs151100121
- Type
- single nucleotide variant
- Location
- chr16:30121850 (GRCh38)
- Gene constraint
- LOEUF 0.935 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.09 · 8 PDB
- Residue 109
- the protein kinase domain
Similar variants
- MAPK3 p.Gly11= Likely benign ★★ same type
- MAPK3 p.Pro336= Benign/Likely benign ★★ same type
- MAPK3 p.Tyr148Cys Likely pathogenic ★ same type
- MAPK3 p.Ala378Asp Uncertain significance ★ ⚠ same type
- MAPK3 p.Arg15Ser Uncertain significance ★ ⚠ same type
- MAPK3 p.Arg242Gln Uncertain significance ★ ⚠ same type
- MAPK3 p.Arg309Gln Uncertain significance ★ ⚠ same type
- MAPK3 p.Arg309Gly 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/mapk3-p-ala109 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown