MAP3K6 p.Ser917=
c.2751C>T · rs145815944 · VCV3053182
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0674%, mid)
Conditions
1
MAP3K6-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.034 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.57 | GERP -2.9, phastCons 0.001 |
| Overall | ||
| CADD | 0.78 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0674%
Middle Eastern · 4/5,938 alleles
Filtering AF
0.0468%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0455%
Overall
0.0391%
623/1,594,396 alleles · ultra-rare
exomes 598/1,442,032 · genomes 25/152,364 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0674% | 1,485 |
| European (non-Finnish) | 0.0502% | 1,990 |
| Remaining individualsnot grpmax-eligible | 0.0227% | 4,396 |
| Admixed American | 0.00952% | 10,508 |
| South Asian | 0.00451% | 22,196 |
| African / African-American | 0.00408% | 24,480 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0035% | 28,570 |
| East Asian | 0.00223% | 44,788 |
| Finnishnot grpmax-eligible | 0.00157% | 63,702 |
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
- MAP3K6
- Protein
- p.Ser917=
- Coding
- c.2751C>T
- MANE Select
- NM_004672
- dbSNP
- rs145815944
- Type
- single nucleotide variant
- Location
- chr1:27358444 (GRCh38)
- Gene constraint
- LOEUF 0.855 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.36
- Residue 917
- the 'disordered' region
Disease context
MAP3K6-related disorder
Similar variants
- MAP3K6 c.1415+9C>T Likely benign same condition
- MAP3K6 c.2584-6C>T Benign same condition
- MAP3K6 c.3259-10C>T Benign same condition
- MAP3K6 c.3711+7C>T Likely benign same condition
- MAP3K6 p.Ala106= Likely benign same condition
- MAP3K6 p.Ala1061Thr Likely benign same condition
- MAP3K6 p.Arg668Gly Benign ⚠ same condition
- MAP3K6 p.Arg913His 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/map3k6-p-ser917 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown