MAP3K3 p.Ser520=
c.1560G>A · rs115890040 · VCV780446
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.04%, afr)
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 -6.1 | GERP -3.4 |
| Overall | ||
| CADD | 2.958 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.04%
African / African-American · 2,283/75,002 alleles
Filtering AF
2.94%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.9%
Overall
0.159%
2,570/1,613,900 alleles · low-frequency
exomes 1,256/1,461,666 · genomes 1,314/152,234 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.04% | 33 |
| Middle Eastern | 0.214% | 466 |
| Remaining individualsnot grpmax-eligible | 0.176% | 568 |
| Admixed American | 0.15% | 667 |
| South Asian | 0.0132% | 7,590 |
| European (non-Finnish) | 0.00517% | 19,344 |
| Finnishnot grpmax-eligible | 0.00157% | 63,848 |
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
- MAP3K3
- Protein
- p.Ser520=
- Coding
- c.1560G>A
- MANE Select
- NM_002401
- dbSNP
- rs115890040
- Type
- single nucleotide variant
- Location
- chr17:63692327 (GRCh38)
- Gene constraint
- LOEUF 0.209 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 67.20 · 6 PDB
- Residue 520
- the protein kinase domain
Similar variants
- MAP3K3 p.Ile441Met Pathogenic/Likely pathogenic ★★ same type
- MAP3K3 p.His133Tyr Uncertain significance ★★ ⚠ same type
- MAP3K3 p.Met524Val Uncertain significance ★★ ⚠ same type
- MAP3K3 c.126+67G>T Benign ★★ same type
- MAP3K3 c.1475-146T>C Benign ★★ same type
- MAP3K3 c.168-35A>G Benign ★★ same type
- MAP3K3 c.268-98T>C Benign ★★ same type
- MAP3K3 c.382-260A>G 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/map3k3-p-ser520 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown