MAP3K6 p.Ala246=
c.738G>A · rs145528948 · VCV2638560
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
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 -1.5 | GERP -3.9 |
| Overall | ||
| CADD | 5.109 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,082 alleles
Filtering AF
0.00884%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00828%
Overall
0.0093%
150/1,612,726 alleles · ultra-rare
exomes 134/1,460,480 · genomes 16/152,246 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,082 |
| Admixed American | 0.015% | 6,665 |
| African / African-American | 0.0147% | 6,813 |
| European (non-Finnish) | 0.0103% | 9,672 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,493 |
| East Asian | 0.00223% | 44,890 |
| South Asian | 0.0011% | 91,048 |
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.Ala246=
- Coding
- c.738G>A
- MANE Select
- NM_004672
- dbSNP
- rs145528948
- Type
- single nucleotide variant
- Location
- chr1:27364043 (GRCh38)
- Gene constraint
- LOEUF 0.855 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.36
Similar variants
- MAP3K6 p.Ala246Val Uncertain significance ★ ⚠ same residue
- 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
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-ala246 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown