MAK p.Asp12=
c.36C>T · rs138352622 · VCV1131015
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00668%, eas)
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 -2.8 | GERP -3.6 |
| Overall | ||
| CADD | 3.561 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00668%
East Asian · 3/44,900 alleles
Filtering AF
0.00402%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00362%
Overall
0.00459%
74/1,613,920 alleles · very rare
exomes 63/1,461,804 · genomes 11/152,116 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00668% | 14,967 |
| South Asian | 0.00549% | 18,215 |
| European (non-Finnish) | 0.00508% | 19,666 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| Admixed American | 0.00333% | 29,999 |
| African / African-American | 0.00134% | 74,880 |
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
- MAK
- Protein
- p.Asp12=
- Coding
- c.36C>T
- MANE Select
- NM_001242957
- dbSNP
- rs138352622
- Type
- single nucleotide variant
- Location
- chr6:10830613 (GRCh38)
- Gene constraint
- LOEUF 0.894 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.74
- Residue 12
- the protein kinase domain; a binding site
Similar variants
- MAK p.Asp12Asn Uncertain significance ★ ⚠ same residue
- MAK p.Asp12fs Pathogenic ★ same residue
- MAK c.101+1G>A Likely pathogenic ★★ same type
- MAK c.156+2T>C Likely pathogenic ★★ same type
- MAK c.831+1G>C Likely pathogenic ★★ same type
- MAK c.832-1G>C Likely pathogenic ★★ same type
- MAK p.Arg166His Pathogenic ★★ same type
- MAK p.Arg272Ter Pathogenic/Likely pathogenic ★★ 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/mak-p-asp12 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown