GEMIN5 p.Pro674=
c.2022C>G · VCV4972789
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0039%, 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 1.1 | GERP -3.3, phastCons 1 |
| Overall | ||
| CADD | 4.208 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0039%
European (non-Finnish) · 46/1,179,968 alleles
Filtering AF
0.00299%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00267%
Overall
0.00291%
47/1,613,876 alleles · very rare
exomes 44/1,461,784 · genomes 3/152,092 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0039% | 25,651 |
| South Asian | 0.0011% | 91,066 |
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
- GEMIN5
- Protein
- p.Pro674=
- Coding
- c.2022C>G
- MANE Select
- NM_015465
- Type
- single nucleotide variant
- Location
- chr5:154911872 (GRCh38)
- Gene constraint
- LOEUF 0.839 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.17 · 16 PDB
- Residue 674
- a β-strand; a UniProt-annotated variant site (in nedcam)
Similar variants
- GEMIN5 p.Arg260Ter Likely pathogenic ★★ same type
- GEMIN5 p.Ile988Phe Likely pathogenic ★★ same type
- GEMIN5 p.Leu1367Pro Likely pathogenic ★★ same type
- GEMIN5 p.Arg1284His Uncertain significance ★★ ⚠ same type
- GEMIN5 p.Glu209Lys Uncertain significance ★★ ⚠ same type
- GEMIN5 p.Leu1127Pro Uncertain significance ★★ ⚠ same type
- GEMIN5 p.Leu1359His Uncertain significance ★★ ⚠ same type
- GEMIN5 p.Leu285Phe 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/gemin5-p-pro674 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown