MAPK8IP3 p.Pro859=
c.2577G>A · rs777435050 · VCV3067363
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00668%, eas)
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 -2.3 | GERP -4.1 |
| Overall | ||
| CADD | 0.635 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00668%
East Asian · 3/44,890 alleles
Filtering AF
0.00286%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00195%
Overall
0.00285%
46/1,612,640 alleles · very rare
exomes 43/1,460,428 · genomes 3/152,212 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00668% | 14,963 |
| South Asian | 0.00659% | 15,180 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,617 |
| European (non-Finnish) | 0.00271% | 36,873 |
| Admixed American | 0.00167% | 59,988 |
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.Pro859=
- Coding
- c.2577G>A
- MANE Select
- NM_001318852
- dbSNP
- rs777435050
- Type
- single nucleotide variant
- Location
- chr16:1766090 (GRCh38)
- Gene constraint
- LOEUF 0.407 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 63.19 · 5 PDB
- Residue 859
- a UniProt-annotated variant site (in nedba)
Similar variants
- MAPK8IP3 p.Pro859Leu Uncertain significance ★ ⚠ same residue
- 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
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-pro859 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown