MAPK8IP3 p.Ala491=
c.1473C>T · rs199824890 · VCV2498636
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.188%, nfe)
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 -0.7 | GERP -3.8, phastCons 0.006 |
| Overall | ||
| CADD | 6.512 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.188%
European (non-Finnish) · 2,224/1,179,974 alleles
Filtering AF
0.182%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.179%
Overall
0.149%
2,401/1,613,660 alleles · rare
exomes 2,235/1,461,304 · genomes 166/152,356 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.188% | 531 |
| Remaining individualsnot grpmax-eligible | 0.112% | 893 |
| Finnishnot grpmax-eligible | 0.105% | 948 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0338% | 2,961 |
| African / African-American | 0.028% | 3,575 |
| Middle Eastern | 0.0165% | 6,062 |
| South Asian | 0.00549% | 18,218 |
| Admixed American | 0.005% | 20,009 |
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.Ala491=
- Coding
- c.1473C>T
- MANE Select
- NM_001318852
- dbSNP
- rs199824890
- Type
- single nucleotide variant
- Location
- chr16:1761239 (GRCh38)
- Gene constraint
- LOEUF 0.407 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 63.19 · 5 PDB
- Residue 491
- a UniProt-annotated variant site (in nedba); the 'interaction with ntrk2' region
Similar variants
- MAPK8IP3 p.Ala491Thr 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-ala491 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown