MAP3K1 p.Ser1282=
c.3846T>G · rs375842337 · VCV1132517
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.01%, amr)
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 0.39 | GERP -4.6, phastCons 1 |
| Overall | ||
| CADD | 7.681 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.01%
Admixed American · 6/59,986 alleles
Filtering AF
0.00428%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00295%
Overall
0.000434%
7/1,613,734 alleles · ultra-rare
exomes 6/1,461,520 · genomes 1/152,214 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.01% | 9,998 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,460 |
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.Ser1282=
- Coding
- c.3846T>G
- MANE Select
- NM_005921
- dbSNP
- rs375842337
- Type
- single nucleotide variant
- Location
- chr5:56884690 (GRCh38)
- Gene constraint
- LOEUF 0.355 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.80 · 1 PDB
- Residue 1282
- the protein kinase domain
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-ser1282 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown