Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Common
common (popmax 92.5%, sas) — too common for a highly-penetrant pathogenic allele
Conditions
1
46,XY sex reversal 6
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 1.1 | GERP -5.2, phastCons 0.99 |
| Overall | ||
| CADD | 8.173 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
92.5%
South Asian · 84,155/91,012 alleles
Filtering AF
91.9%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 91.7%
Overall
86.6%
1,393,360/1,609,570 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 92.5% | 1 |
| Finnishnot grpmax-eligible | 89.8% | 1 |
| European (non-Finnish) | 87.8% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 87.3% | 1 |
| Remaining individualsnot grpmax-eligible | 85.7% | 1 |
| Middle Eastern | 84.3% | 1 |
| African / African-American | 79.4% | 1 |
| Amishnot grpmax-eligible | 79.2% | 1 |
| Admixed American | 71.7% | 1 |
| East Asian | 69.7% | 1 |
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
- MAP3K1
- Protein
- p.Thr428=
- Coding
- c.1284G>A
- MANE Select
- NM_005921
- dbSNP
- rs832575
- Type
- single nucleotide variant
- Location
- chr5:56865960 (GRCh38)
- Gene constraint
- LOEUF 0.355 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.80 · 1 PDB
- Residue 428
- the 'disordered' region
Similar variants
- MAP3K1 p.Arg186Gly Pathogenic/Likely pathogenic ★★ ⚠ same condition
- MAP3K1 p.Ala594Ser Uncertain significance ★★ ⚠ same condition
- MAP3K1 p.Arg204Lys Uncertain significance ★★ ⚠ same condition
- MAP3K1 p.Gln548Glu Uncertain significance ★★ ⚠ same condition
- MAP3K1 c.1035+12C>T Likely benign ★★ same condition
- MAP3K1 c.1687-46C>G Benign ★★ same condition
- MAP3K1 c.2179+16T>G Benign/Likely benign ★★ same condition
- MAP3K1 c.3820-11A>G Benign ★★ same condition
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/map3k1-p-thr428 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown