MAK p.Pro373=
c.1119G>A · rs1011259942 · VCV1161582
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00891%, eas)
Conditions
1
inherited retinal dystrophy
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 -2.3 | GERP -3.4 |
| Overall | ||
| CADD | 0.613 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00891%
East Asian · 4/44,886 alleles
Filtering AF
0.00298%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0018%
Overall
0.00136%
22/1,613,710 alleles · very rare
exomes 17/1,461,562 · genomes 5/152,148 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00891% | 11,222 |
| South Asian | 0.00439% | 22,764 |
| African / African-American | 0.00133% | 74,918 |
| European (non-Finnish) | 0.0011% | 90,752 |
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.Pro373=
- Coding
- c.1119G>A
- MANE Select
- NM_001242957
- dbSNP
- rs1011259942
- Type
- single nucleotide variant
- Location
- chr6:10796022 (GRCh38)
- Gene constraint
- LOEUF 0.894 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.74
- Residue 373
- the 'disordered' region
Similar variants
- MAK p.Pro373Leu Uncertain significance ★★ ⚠ same residue
- MAK p.Asn130His Likely pathogenic ★★ same condition
- MAK p.Gln351Ter Pathogenic/Likely pathogenic ★★ same condition
- MAK p.Glu263Lys Uncertain significance ★★ ⚠ same condition
- MAK p.His123Leu Uncertain significance ★★ ⚠ same condition
- MAK p.Ile189Val Uncertain significance ★★ ⚠ same condition
- MAK p.Lys402Thr Uncertain significance ★★ ⚠ same condition
- MAK p.Met425Val Uncertain significance ★★ ⚠ same condition
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-pro373 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown