MAP3K20 p.Pro728=
c.2184T>C · rs376883135 · VCV1560630
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0467%, 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 -0.47 | GERP -5.4 |
| Overall | ||
| CADD | 4.127 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0467%
African / African-American · 35/74,896 alleles
Filtering AF
0.0345%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0303%
Overall
0.00223%
36/1,613,854 alleles · ultra-rare
exomes 19/1,461,714 · genomes 17/152,140 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0467% | 2,140 |
| Admixed American | 0.00167% | 59,984 |
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.Pro728=
- Coding
- c.2184T>C
- MANE Select
- NM_016653
- dbSNP
- rs376883135
- Type
- single nucleotide variant
- Location
- chr2:173266531 (GRCh38)
- Gene constraint
- LOEUF 0.569 · pLI 0.14 (gnomAD)
- Structure
- AlphaFold pLDDT 69.15 · 8 PDB
- Residue 728
- a UniProt-annotated variant site (in cnm6; decrease of protein abundance); the 'disordered' region
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-pro728 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown