MAK p.Pro520=
c.1560C>T · rs756785609 · VCV1093858
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00329%, sas)
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 |
|---|---|---|
| Pangolin | Δ0.32 | gain · loss 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.85 | GERP -1.3, phastCons 0.26 |
| Overall | ||
| CADD | 4.234 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00329%
South Asian · 3/91,070 alleles
Filtering AF
0.00111%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0009%
Overall
0.00143%
23/1,613,712 alleles · very rare
exomes 21/1,461,516 · genomes 2/152,196 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00329% | 30,357 |
| European (non-Finnish) | 0.0017% | 58,990 |
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.Pro520=
- Coding
- c.1560C>T
- MANE Select
- NM_001242957
- dbSNP
- rs756785609
- Type
- single nucleotide variant
- Location
- chr6:10775365 (GRCh38)
- Gene constraint
- LOEUF 0.894 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.74
- Residue 520
- a UniProt-annotated variant site (in)
Similar variants
- MAK p.Pro520Ser Benign/Likely benign ★★ 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-pro520 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown