MAP3K20 p.Asp558=
c.1674T>C · rs16861466 · VCV1231214
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 9.02%, amr) — too common for a highly-penetrant pathogenic allele
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 0.33 | GERP -5.4, phastCons 0.97 |
| Overall | ||
| CADD | 0.953 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
9.02%
Admixed American · 5,359/59,380 alleles
Filtering AF
8.82%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 8.74%
Overall
4.58%
73,791/1,612,264 alleles · common
exomes 67,751/1,459,950 · genomes 6,040/152,314 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 9.02% | 11 |
| East Asian | 5.36% | 19 |
| Remaining individualsnot grpmax-eligible | 4.95% | 20 |
| South Asian | 4.66% | 21 |
| European (non-Finnish) | 4.55% | 22 |
| Amishnot grpmax-eligible | 4.51% | 22 |
| Finnishnot grpmax-eligible | 4.39% | 23 |
| Middle Eastern | 4.28% | 23 |
| Ashkenazi Jewishnot grpmax-eligible | 3.86% | 26 |
| African / African-American | 1.01% | 99 |
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
- MAP3K20
- Protein
- p.Asp558=
- Coding
- c.1674T>C
- MANE Select
- NM_016653
- dbSNP
- rs16861466
- Type
- single nucleotide variant
- Location
- chr2:173263867 (GRCh38)
- Gene constraint
- LOEUF 0.569 · pLI 0.14 (gnomAD)
- Structure
- AlphaFold pLDDT 69.15 · 8 PDB
- Residue 558
- a UniProt-annotated variant site (in cnm6; decrease of protein abundance)
Similar variants
- MAP3K20 p.Arg250Trp Uncertain significance ★★ ⚠ same type
- MAP3K20 p.Arg293Lys Uncertain significance ★★ same type
- MAP3K20 p.Arg536Lys Uncertain significance ★★ ⚠ same type
- MAP3K20 p.Arg634Gly Uncertain significance ★★ ⚠ same type
- MAP3K20 p.Arg774Trp Uncertain significance ★★ ⚠ same type
- MAP3K20 p.Arg795His Uncertain significance ★★ ⚠ same type
- MAP3K20 p.Gln632Ter Uncertain significance ★★ same type
- MAP3K20 p.Glu405Gly 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/map3k20-p-asp558 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown