MAP4K3 p.Leu599=
c.1795C>T · rs201933119 · VCV3123101
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.101%, eas)
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 |
|---|---|---|
| Pangolin | Δ0.27 | loss · gain 0.03 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 0.32, phastCons 1 |
| Overall | ||
| CADD | 15.84 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.101%
East Asian · 45/44,738 alleles
Filtering AF
0.0772%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.069%
Overall
0.00298%
48/1,612,398 alleles · rare
exomes 44/1,460,258 · genomes 4/152,140 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.101% | 994 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,217 |
| South Asian | 0.0011% | 90,892 |
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
- MAP4K3
- Protein
- p.Leu599=
- Coding
- c.1795C>T
- MANE Select
- NM_003618
- dbSNP
- rs201933119
- Type
- single nucleotide variant
- Location
- chr2:39272542 (GRCh38)
- Gene constraint
- LOEUF 0.792 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.96 · 1 PDB
- Residue 599
- the cnh domain
Similar variants
- MAP4K3 p.Ala253Thr Uncertain significance ★ ⚠ same type
- MAP4K3 p.Ala310Val Uncertain significance ★ ⚠ same type
- MAP4K3 p.Ala391Glu Uncertain significance ★ ⚠ same type
- MAP4K3 p.Ala429Val Uncertain significance ★ ⚠ same type
- MAP4K3 p.Ala621Thr Uncertain significance ★ ⚠ same type
- MAP4K3 p.Ala664Pro Uncertain significance ★ ⚠ same type
- MAP4K3 p.Ala75Thr Uncertain significance ★ ⚠ same type
- MAP4K3 p.Arg482Lys 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/map4k3-p-leu599 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown