MAP3K6 p.Pro489=
c.1467C>T · rs373729597 · VCV3035484
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.048%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.049 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.92 | GERP 0.43, phastCons 0.33 |
| Overall | ||
| CADD | 4.284 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.048%
South Asian · 43/89,544 alleles
Filtering AF
0.0431%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0418%
Overall
0.0394%
631/1,601,458 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.048% | 2,082 |
| European (non-Finnish) | 0.0464% | 2,157 |
| Middle Eastern | 0.0334% | 2,997 |
| Remaining individualsnot grpmax-eligible | 0.0259% | 3,868 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0243% | 4,113 |
| Admixed American | 0.0241% | 4,146 |
| African / African-American | 0.00535% | 18,681 |
| Finnishnot grpmax-eligible | 0.00158% | 63,188 |
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.Pro489=
- Coding
- c.1467C>T
- MANE Select
- NM_004672
- dbSNP
- rs373729597
- Type
- single nucleotide variant
- Location
- chr1:27361816 (GRCh38)
- Gene constraint
- LOEUF 0.855 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.36
Similar variants
- MAP3K6 c.1256-2A>G Likely benign ★★ same type
- MAP3K6 c.2915+9A>T Benign ★★ same type
- MAP3K6 p.Ala405= Benign/Likely benign ★★ same type
- MAP3K6 p.Arg499Cys Benign ★★ same type
- MAP3K6 p.Asn622Lys Benign ★★ same type
- MAP3K6 p.Gln1142Arg Benign ★★ same type
- MAP3K6 p.Glu248= Likely benign ★★ same type
- MAP3K6 p.Leu1249= Benign ★★ same type
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-pro489 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown