GEMIN4 p.Pro557=
c.1671G>A · rs372759771 · VCV748939
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0481%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -4.6 |
| Overall | ||
| CADD | 0.016 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0481%
African / African-American · 36/74,912 alleles
Filtering AF
0.0357%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0314%
Overall
0.00397%
64/1,613,706 alleles · ultra-rare
exomes 40/1,461,562 · genomes 24/152,144 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0481% | 2,081 |
| South Asian | 0.00988% | 10,121 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,606 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,229 |
| Admixed American | 0.00167% | 59,998 |
| European (non-Finnish) | 0.00127% | 78,660 |
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
- GEMIN4
- Protein
- p.Pro557=
- Coding
- c.1671G>A
- MANE Select
- NM_015721
- dbSNP
- rs372759771
- Type
- single nucleotide variant
- Location
- chr17:746372 (GRCh38)
- Gene constraint
- LOEUF 0.947 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.54
Similar variants
- GEMIN4 p.Pro557Leu Uncertain significance ★ ⚠ same residue
- GEMIN4 p.Trp818Arg Pathogenic/Likely pathogenic ★★ same type
- GEMIN4 p.Ala186Val Uncertain significance ★★ ⚠ same type
- GEMIN4 p.Arg91Gln Uncertain significance ★★ ⚠ same type
- GEMIN4 p.Gln1032Ter Uncertain significance ★★ same type
- GEMIN4 p.Gly814Glu Uncertain significance ★★ ⚠ same type
- GEMIN4 p.Ile406Val Uncertain significance ★★ ⚠ same type
- GEMIN4 p.Leu178Val Uncertain significance ★★ ⚠ 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/gemin4-p-pro557 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown