MAPK1 p.Cys40=
c.120C>T · VCV4103713
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0524%, afr)
Conditions
1
Inborn genetic diseases
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 3.4 | GERP 0.92, phastCons 1 |
| Overall | ||
| CADD | 12.63 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0524%
African / African-American · 39/74,386 alleles
Filtering AF
0.0394%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0348%
Overall
0.00324%
52/1,604,572 alleles · ultra-rare
exomes 27/1,452,326 · genomes 25/152,246 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0524% | 1,907 |
| Admixed American | 0.00696% | 14,360 |
| Remaining individualsnot grpmax-eligible | 0.00322% | 31,053 |
| European (non-Finnish) | 0.000595% | 168,138 |
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.Cys40=
- Coding
- c.120C>T
- MANE Select
- NM_002745
- Type
- single nucleotide variant
- Location
- chr22:21807846 (GRCh38)
- Gene constraint
- LOEUF 0.377 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 90.99 · 157 PDB
- Residue 40
- the protein kinase domain; a β-strand
Similar variants
- MAPK1 p.Arg135Thr Likely pathogenic ★★ same condition
- MAPK1 p.Asn297Ser Uncertain significance ★ ⚠ same condition
- MAPK1 p.Lys164Gln Uncertain significance ★ ⚠ same condition
- MAPK1 p.Met13Ile Uncertain significance ★ ⚠ same condition
- MAPK1 p.Ala174Val 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
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-cys40 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown