MAK p.Phe415=
c.1245C>T · rs115185609 · VCV709229
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.52%, 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 -4.9 | GERP -3.6 |
| Overall | ||
| CADD | 2.375 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.52%
African / African-American · 1,136/74,978 alleles
Filtering AF
1.44%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.41%
Overall
0.0845%
1,364/1,613,884 alleles · low-frequency
exomes 719/1,461,746 · genomes 645/152,138 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.52% | 66 |
| Remaining individualsnot grpmax-eligible | 0.163% | 613 |
| Admixed American | 0.132% | 760 |
| Middle Eastern | 0.033% | 3,031 |
| South Asian | 0.0242% | 4,139 |
| East Asian | 0.00223% | 44,876 |
| European (non-Finnish) | 0.00186% | 53,631 |
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.Phe415=
- Coding
- c.1245C>T
- MANE Select
- NM_001242957
- dbSNP
- rs115185609
- Type
- single nucleotide variant
- Location
- chr6:10791746 (GRCh38)
- Gene constraint
- LOEUF 0.894 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.74
Similar variants
- MAK p.Phe415fs 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
- MAK p.Arg3Ter 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-phe415 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown