MAPK8IP3 p.Lys540=
c.1620G>A · rs8052407 · VCV3025634
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.752%, afr)
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 | GERP -3.8, phastCons 1 |
| Overall | ||
| CADD | 7.873 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.752%
African / African-American · 564/74,966 alleles
Filtering AF
0.701%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.681%
Overall
0.0396%
637/1,609,296 alleles · rare
exomes 300/1,456,926 · genomes 337/152,370 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.752% | 133 |
| Remaining individualsnot grpmax-eligible | 0.0562% | 1,779 |
| Admixed American | 0.0539% | 1,856 |
| Middle Eastern | 0.0165% | 6,048 |
| European (non-Finnish) | 0.000424% | 235,603 |
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
- MAPK8IP3
- Protein
- p.Lys540=
- Coding
- c.1620G>A
- MANE Select
- NM_001318852
- dbSNP
- rs8052407
- Type
- single nucleotide variant
- Location
- chr16:1762431 (GRCh38)
- Gene constraint
- LOEUF 0.407 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 63.19 · 5 PDB
- Residue 540
- the rh2 domain; a UniProt-annotated variant site (in nedba); an α-helix
Similar variants
- MAPK8IP3 p.Arg1147Cys Pathogenic/Likely pathogenic ★★ same type
- MAPK8IP3 p.Arg579Cys Pathogenic/Likely pathogenic ★★ same type
- MAPK8IP3 p.Gln468Ter Pathogenic/Likely pathogenic ★★ same type
- MAPK8IP3 p.Glu27Ter Likely pathogenic ★★ same type
- MAPK8IP3 p.Glu462Gly Likely pathogenic ★★ same type
- MAPK8IP3 p.Leu445Pro Likely pathogenic ★★ same type
- MAPK8IP3 p.Tyr37Ter Likely pathogenic ★★ same type
- MAPK8IP3 c.1898+5G>A 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/mapk8ip3-p-lys540 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown