MAP3K20 p.Ile421=
c.1263T>C · rs3739103 · VCV1260904
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 52.8%, eas) — 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 | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1 | GERP -0.95, phastCons 0.99 |
| Overall | ||
| CADD | 6.14 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
52.8%
East Asian · 23,619/44,720 alleles
Filtering AF
52.3%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 52%
Overall
4.77%
76,769/1,609,932 alleles · common
exomes 67,361/1,457,714 · genomes 9,408/152,218 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 52.8% | 2 |
| Admixed American | 11.7% | 9 |
| Finnishnot grpmax-eligible | 6.9% | 14 |
| Remaining individualsnot grpmax-eligible | 5.96% | 17 |
| African / African-American | 5.47% | 18 |
| Middle Eastern | 3.19% | 31 |
| South Asian | 3.11% | 32 |
| European (non-Finnish) | 2.57% | 39 |
| Ashkenazi Jewishnot grpmax-eligible | 2.56% | 39 |
| Amishnot grpmax-eligible | 1.86% | 54 |
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.Ile421=
- Coding
- c.1263T>C
- MANE Select
- NM_016653
- dbSNP
- rs3739103
- Type
- single nucleotide variant
- Location
- chr2:173238432 (GRCh38)
- Gene constraint
- LOEUF 0.569 · pLI 0.14 (gnomAD)
- Structure
- AlphaFold pLDDT 69.15 · 8 PDB
- Residue 421
- 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-ile421 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown