MAP3K1 p.Arg697=
c.2091C>T · rs372638992 · VCV3039404
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0991%, mid)
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 -0.34 | GERP 0.24, phastCons 0.099 |
| Overall | ||
| CADD | 7.721 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0991%
Middle Eastern · 6/6,054 alleles
Filtering AF
0.0432%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0295%
Overall
0.00496%
80/1,612,706 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0991% | 1,009 |
| European (non-Finnish) | 0.0056% | 17,863 |
| South Asian | 0.00439% | 22,766 |
| Admixed American | 0.00333% | 29,988 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,218 |
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.Arg697=
- Coding
- c.2091C>T
- MANE Select
- NM_005921
- dbSNP
- rs372638992
- Type
- single nucleotide variant
- Location
- chr5:56880714 (GRCh38)
- Gene constraint
- LOEUF 0.355 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.80 · 1 PDB
- Residue 697
- an α-helix
Similar variants
- MAP3K1 p.Arg697His Uncertain significance ★ ⚠ same residue
- 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
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-arg697 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown