MAK p.Pro325=
c.975G>A · rs145014649 · VCV199064
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.141%, nfe)
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 -1.5 | GERP -3.4 |
| Overall | ||
| CADD | 2.095 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.141%
European (non-Finnish) · 1,658/1,180,028 alleles
Filtering AF
0.135%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.133%
Overall
0.114%
1,834/1,614,150 alleles · rare
exomes 1,731/1,461,888 · genomes 103/152,262 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.141% | 712 |
| Remaining individualsnot grpmax-eligible | 0.125% | 801 |
| South Asian | 0.0549% | 1,821 |
| Middle Eastern | 0.0495% | 2,021 |
| African / African-American | 0.024% | 4,168 |
| Admixed American | 0.0183% | 5,456 |
| East Asian | 0.0156% | 6,412 |
| Finnishnot grpmax-eligible | 0.0109% | 9,147 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00675% | 14,804 |
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.Pro325=
- Coding
- c.975G>A
- MANE Select
- NM_001242957
- dbSNP
- rs145014649
- Type
- single nucleotide variant
- Location
- chr6:10796166 (GRCh38)
- Gene constraint
- LOEUF 0.894 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.74
- Residue 325
- a UniProt-annotated variant site (in)
Similar variants
- MAK p.Pro325Leu Likely benign ★★ same residue
- MAK p.Pro325Arg Uncertain significance ★ ⚠ 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-pro325 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown