MAPK1 p.Ala325=
c.975C>T · VCV3904944
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.33%, 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 -0.55 | GERP -3.8 |
| Overall | ||
| CADD | 6.843 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.33%
African / African-American · 990/74,660 alleles
Filtering AF
1.26%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.23%
Overall
0.0746%
1,192/1,598,104 alleles · low-frequency
exomes 563/1,445,890 · genomes 629/152,214 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.33% | 75 |
| Middle Eastern | 0.116% | 861 |
| Admixed American | 0.114% | 879 |
| Remaining individualsnot grpmax-eligible | 0.079% | 1,265 |
| European (non-Finnish) | 0.00626% | 15,975 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00339% | 29,492 |
| South Asian | 0.00331% | 30,189 |
| Finnishnot grpmax-eligible | 0.00157% | 63,688 |
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
- MAPK1
- Protein
- p.Ala325=
- Coding
- c.975C>T
- MANE Select
- NM_002745
- Type
- single nucleotide variant
- Location
- chr22:21769312 (GRCh38)
- Gene constraint
- LOEUF 0.377 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 90.99 · 157 PDB
- Residue 325
- an α-helix
Similar variants
- MAPK1 p.Ala174Val Pathogenic ★★ ⚠ same type
- MAPK1 p.Arg135Thr Likely pathogenic ★★ same type
- MAPK1 p.Asp318Asn Pathogenic/Likely pathogenic ★★ same type
- MAPK1 p.Asp318Gly Pathogenic ★★ same type
- MAPK1 p.Glu322Gln Pathogenic/Likely pathogenic ★★ same type
- MAPK1 p.His80Tyr Pathogenic ★★ same type
- MAPK1 p.Asn27Asp Uncertain significance ★★ ⚠ same type
- MAPK1 p.Asn82Asp Likely pathogenic ★ 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/mapk1-p-ala325 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown