MAP3K6 p.Ala405=
c.1215C>T · rs55972073 · VCV718726
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.54%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.254 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.54 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -13 | GERP -3 |
| Overall | ||
| CADD | 0.175 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.54%
African / African-American · 1,158/74,952 alleles
Filtering AF
1.47%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.44%
Overall
0.0953%
1,530/1,606,214 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.54% | 65 |
| Admixed American | 0.115% | 868 |
| Remaining individualsnot grpmax-eligible | 0.0884% | 1,131 |
| Middle Eastern | 0.0828% | 1,208 |
| European (non-Finnish) | 0.0202% | 4,940 |
| South Asian | 0.00334% | 29,951 |
| Finnishnot grpmax-eligible | 0.00315% | 31,716 |
| East Asian | 0.00224% | 44,668 |
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.Ala405=
- Coding
- c.1215C>T
- MANE Select
- NM_004672
- dbSNP
- rs55972073
- Type
- single nucleotide variant
- Location
- chr1:27362681 (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.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
- MAP3K6 p.Pro946Leu Benign/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-ala405 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown