MAP3K1 p.Pro1497=
c.4491T>C · VCV4797586
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.148%, afr)
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 0.7 | GERP 0.23, phastCons 1 |
| Overall | ||
| CADD | 8.667 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.148%
African / African-American · 111/75,044 alleles
Filtering AF
0.126%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.117%
Overall
0.00768%
124/1,613,940 alleles · rare
exomes 66/1,461,620 · genomes 58/152,320 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.148% | 676 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| Admixed American | 0.00333% | 30,001 |
| European (non-Finnish) | 0.000678% | 147,481 |
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.Pro1497=
- Coding
- c.4491T>C
- MANE Select
- NM_005921
- Type
- single nucleotide variant
- Location
- chr5:56893632 (GRCh38)
- Gene constraint
- LOEUF 0.355 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.80 · 1 PDB
- Residue 1497
- 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-pro1497 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown