MAP3K8 p.Pro373=
c.1119C>T · VCV4705577
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
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 -0.62 | GERP 0.66, phastCons 0.009 |
| Overall | ||
| CADD | 9.039 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,058 alleles
Filtering AF
0.00582%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00242%
Overall
0.00186%
30/1,614,136 alleles · ultra-rare
exomes 27/1,461,888 · genomes 3/152,248 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,029 |
| South Asian | 0.00659% | 15,181 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,251 |
| East Asian | 0.00223% | 44,878 |
| European (non-Finnish) | 0.00161% | 62,107 |
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.Pro373=
- Coding
- c.1119C>T
- MANE Select
- NM_005204
- Type
- single nucleotide variant
- Location
- chr10:30459347 (GRCh38)
- Gene constraint
- LOEUF 0.58 · pLI 0.73 (gnomAD)
- Structure
- AlphaFold pLDDT 74.13 · 3 PDB
- Residue 373
- the protein kinase domain; a turn
Similar variants
- MAP3K8 p.Pro373Ala Uncertain significance ★ same residue
- 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
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-pro373 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown