MAPK8IP3 p.Asp737=
c.2211T>C · rs2294618 · VCV1185435
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 31.9%, eas) — too common for a highly-penetrant pathogenic allele
Conditions
1
neurodevelopmental disorder with or without variable brain abnormalities; NEDBA
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 1.4 | GERP -0.24, phastCons 1 |
| Overall | ||
| CADD | 8.408 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
31.9%
East Asian · 14,100/44,154 alleles
Filtering AF
31.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 31.3%
Overall
13.8%
221,019/1,597,666 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 31.9% | 3 |
| South Asian | 18.9% | 5 |
| Finnishnot grpmax-eligible | 15.2% | 7 |
| European (non-Finnish) | 13.5% | 7 |
| Remaining individualsnot grpmax-eligible | 13.3% | 8 |
| Ashkenazi Jewishnot grpmax-eligible | 13.1% | 8 |
| Middle Eastern | 11.1% | 9 |
| Admixed American | 9.37% | 11 |
| Amishnot grpmax-eligible | 8.99% | 11 |
| African / African-American | 4.91% | 20 |
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.Asp737=
- Coding
- c.2211T>C
- MANE Select
- NM_001318852
- dbSNP
- rs2294618
- Type
- single nucleotide variant
- Location
- chr16:1764390 (GRCh38)
- Gene constraint
- LOEUF 0.407 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 63.19 · 5 PDB
- Residue 737
- a UniProt-annotated variant site (in nedba); the 'disordered' region
Similar variants
- MAPK8IP3 p.Arg1147Cys Pathogenic/Likely pathogenic ★★ same condition
- MAPK8IP3 p.Arg579Cys Pathogenic/Likely pathogenic ★★ same condition
- MAPK8IP3 p.Gln468Ter Pathogenic/Likely pathogenic ★★ same condition
- MAPK8IP3 p.Glu27Ter Likely pathogenic ★★ same condition
- MAPK8IP3 p.Glu462Gly Likely pathogenic ★★ same condition
- MAPK8IP3 p.Leu445Pro Likely pathogenic ★★ same condition
- MAPK8IP3 p.Tyr37Ter Likely pathogenic ★★ same condition
- MAPK8IP3 p.Ala817Asp Uncertain significance ★★ ⚠ same condition
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-asp737 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown