MAPK8IP3 p.Asp633=
c.1899C>T · rs200312072 · VCV2645921
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0955%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.45 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.44 | GERP -2.6, phastCons 0.094 |
| Overall | ||
| CADD | 15.02 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0955%
Admixed American · 52/54,456 alleles
Filtering AF
0.0807%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0789%
Overall
0.072%
1,126/1,563,498 alleles · ultra-rare
exomes 1,030/1,411,144 · genomes 96/152,354 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0955% | 1,047 |
| European (non-Finnish) | 0.0852% | 1,174 |
| Remaining individualsnot grpmax-eligible | 0.0681% | 1,469 |
| Middle Eastern | 0.067% | 1,492 |
| Finnishnot grpmax-eligible | 0.0512% | 1,954 |
| South Asian | 0.0128% | 7,795 |
| African / African-American | 0.0068% | 14,704 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00352% | 28,384 |
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.Asp633=
- Coding
- c.1899C>T
- MANE Select
- NM_001318852
- dbSNP
- rs200312072
- Type
- single nucleotide variant
- Location
- chr16:1763657 (GRCh38)
- Gene constraint
- LOEUF 0.407 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 63.19 · 5 PDB
- Residue 633
- a UniProt-annotated variant site (in nedba)
Similar variants
- MAPK8IP3 p.Asp633Glu Conflicting classifications of pathogenicity ★ ⚠ 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-asp633 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown