Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.135%, sas)
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 2.9 | GERP -3.3, phastCons 1 |
| Overall | ||
| CADD | 11.52 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.135%
South Asian · 120/88,728 alleles
Filtering AF
0.116%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.108%
Overall
0.0269%
398/1,478,434 alleles · rare
exomes 256/1,332,100 · genomes 142/146,334 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.135% | 739 |
| Finnishnot grpmax-eligible | 0.0436% | 2,292 |
| African / African-American | 0.0395% | 2,529 |
| Remaining individualsnot grpmax-eligible | 0.0314% | 3,186 |
| European (non-Finnish) | 0.0186% | 5,363 |
| Admixed American | 0.0108% | 9,298 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00795% | 12,575 |
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
- MAP2K3
- Protein
- p.Leu319=
- Coding
- c.957G>C
- MANE Select
- NM_145109
- dbSNP
- rs1657688
- Type
- single nucleotide variant
- Location
- chr17:21313534 (GRCh38)
- Gene constraint
- LOEUF 0.993 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.13
- Residue 319
- the protein kinase domain
Similar variants
- MAP2K3 p.Leu215Trp Uncertain significance ★★ ⚠ same type
- MAP2K3 c.568+10C>T Benign ★★ same type
- MAP2K3 p.Ala220= Benign ★★ same type
- MAP2K3 p.Ala225= Likely benign ★★ same type
- MAP2K3 p.Leu25= Benign ★★ same type
- MAP2K3 p.Pro40Thr Benign ★★ same type
- MAP2K3 p.Ser286= Likely benign ★★ same type
- MAP2K3 p.Thr39Ile Likely benign ★★ 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/map2k3-p-leu319 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown