Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.23%, 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 -1.9 | GERP -3.6 |
| Overall | ||
| CADD | 6.673 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.23%
Middle Eastern · 135/6,062 alleles
Filtering AF
1.92%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.81%
Overall
0.274%
4,416/1,613,914 alleles · low-frequency
exomes 3,998/1,461,706 · genomes 418/152,208 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 2.23% | 45 |
| Ashkenazi Jewishnot grpmax-eligible | 0.504% | 199 |
| Admixed American | 0.473% | 211 |
| Remaining individualsnot grpmax-eligible | 0.322% | 311 |
| Finnishnot grpmax-eligible | 0.281% | 356 |
| European (non-Finnish) | 0.276% | 363 |
| African / African-American | 0.136% | 735 |
| South Asian | 0.123% | 813 |
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.Pro336=
- Coding
- c.1008G>A
- MANE Select
- NM_002746
- dbSNP
- rs1143695
- Type
- single nucleotide variant
- Location
- chr16:30116903 (GRCh38)
- Gene constraint
- LOEUF 0.935 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.09 · 8 PDB
- Residue 336
- an α-helix
Similar variants
- MAPK3 p.Pro336Ser Uncertain significance ★ same residue
- MAPK3 p.Gly11= 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-pro336 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown