MAPK8IP3 p.Pro619=
c.1857G>A · VCV4927336
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00636%, nfe)
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 1.3 | GERP -4.2, phastCons 1 |
| Overall | ||
| CADD | 7.854 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00636%
European (non-Finnish) · 75/1,179,998 alleles
Filtering AF
0.00519%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00474%
Overall
0.00477%
77/1,612,860 alleles · very rare
exomes 76/1,460,614 · genomes 1/152,246 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00636% | 15,733 |
| East Asian | 0.00223% | 44,894 |
| South Asian | 0.0011% | 91,090 |
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.Pro619=
- Coding
- c.1857G>A
- MANE Select
- NM_001318852
- Type
- single nucleotide variant
- Location
- chr16:1762965 (GRCh38)
- Gene constraint
- LOEUF 0.407 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 63.19 · 5 PDB
- Residue 619
- a UniProt-annotated variant site (in nedba)
Similar variants
- MAPK8IP3 p.Pro619Ser 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-pro619 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown