MAP3K8 p.Leu438=
c.1314C>T · rs372877014 · VCV1428415
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00407%, 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 -4.9 | GERP -3.2 |
| Overall | ||
| CADD | 0.254 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00407%
European (non-Finnish) · 48/1,179,796 alleles
Filtering AF
0.00315%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00279%
Overall
0.00322%
52/1,613,440 alleles · very rare
exomes 44/1,461,210 · genomes 8/152,230 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00407% | 24,579 |
| Admixed American | 0.00334% | 29,969 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,234 |
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.Leu438=
- Coding
- c.1314C>T
- MANE Select
- NM_005204
- dbSNP
- rs372877014
- Type
- single nucleotide variant
- Location
- chr10:30460746 (GRCh38)
- Gene constraint
- LOEUF 0.58 · pLI 0.73 (gnomAD)
- Structure
- AlphaFold pLDDT 74.13 · 3 PDB
- Residue 438
- a UniProt-annotated variant site (in oncogenic form)
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-leu438 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown