MAP3K8 p.Asp352=
c.1056C>T · rs137991584 · VCV1531612
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.405%, afr)
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 -1.5 | GERP -0.52 |
| Overall | ||
| CADD | 4.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.405%
African / African-American · 304/75,040 alleles
Filtering AF
0.368%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.353%
Overall
0.0396%
640/1,614,180 alleles · rare
exomes 417/1,461,874 · genomes 223/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.405% | 247 |
| Admixed American | 0.055% | 1,819 |
| Middle Eastern | 0.0496% | 2,018 |
| Remaining individualsnot grpmax-eligible | 0.0432% | 2,315 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0372% | 2,691 |
| European (non-Finnish) | 0.0221% | 4,521 |
| South Asian | 0.0011% | 91,080 |
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
- MAP3K8
- Protein
- p.Asp352=
- Coding
- c.1056C>T
- MANE Select
- NM_005204
- dbSNP
- rs137991584
- Type
- single nucleotide variant
- Location
- chr10:30459284 (GRCh38)
- Gene constraint
- LOEUF 0.58 · pLI 0.73 (gnomAD)
- Structure
- AlphaFold pLDDT 74.13 · 3 PDB
- Residue 352
- the protein kinase domain; an α-helix
Similar variants
- MAP3K8 p.Ala35Ser Uncertain significance ★★ ⚠ same type
- MAP3K8 p.Ala450Thr Uncertain significance ★★ same type
- MAP3K8 p.Arg392Gly Uncertain significance ★★ ⚠ same type
- MAP3K8 p.Arg408Ser Uncertain significance ★★ ⚠ same type
- MAP3K8 p.Asn54Asp Uncertain significance ★★ ⚠ same type
- MAP3K8 p.Gly67Asp Uncertain significance ★★ ⚠ same type
- MAP3K8 p.Ile190Val Uncertain significance ★★ ⚠ same type
- MAP3K8 p.Met277Ile Uncertain significance ★★ ⚠ 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/map3k8-p-asp352 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown