MAK p.Asp405=
c.1215T>C · rs148549681 · VCV1985801
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.044%, afr)
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 -3.6 | GERP -3.6 |
| Overall | ||
| CADD | 0.169 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.044%
African / African-American · 33/74,916 alleles
Filtering AF
0.0322%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0281%
Overall
0.00217%
35/1,613,952 alleles · ultra-rare
exomes 9/1,461,842 · genomes 26/152,110 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.044% | 2,270 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
| European (non-Finnish) | 8.47e-05% | 1,179,974 |
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.Asp405=
- Coding
- c.1215T>C
- MANE Select
- NM_001242957
- dbSNP
- rs148549681
- Type
- single nucleotide variant
- Location
- chr6:10791776 (GRCh38)
- Gene constraint
- LOEUF 0.894 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.74
Similar variants
- 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
- MAK p.Arg3Ter Pathogenic/Likely pathogenic ★★ same type
- MAK p.Asn130His 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-asp405 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown