GORAB p.Pro86Leu
c.257C>T · rs374614330 · VCV1448618
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0414%, afr)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.217 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 2.8 | GERP 1.5, phastCons 0.14 |
| Regional constraint | o/e 1.01 | unconstrained · MANE · 20 kb · p 0.84 · regional, not allelic |
| Overall | ||
| CADD | 21.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0414%
African / African-American · 31/74,906 alleles
Filtering AF
0.0299%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.026%
Overall
0.00248%
40/1,613,978 alleles · ultra-rare
exomes 25/1,461,834 · genomes 15/152,144 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0414% | 2,416 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
| Finnishnot grpmax-eligible | 0.00156% | 64,032 |
| European (non-Finnish) | 0.000593% | 168,571 |
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
- GORAB
- Protein
- p.Pro86Leu
- Coding
- c.257C>T
- MANE Select
- NM_152281
- dbSNP
- rs374614330
- Type
- single nucleotide variant
- Location
- chr1:170539405 (GRCh38)
- Gene constraint
- LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 71.86
- Residue 86
- the 'disordered' region
Similar variants
- GORAB p.Pro86= Likely benign ★ same residue
- GORAB p.Arg35Ter Pathogenic ★★ same condition
- GORAB p.Pro86fs Pathogenic/Likely pathogenic ★★ same residue
- GORAB c.-21G>A Uncertain significance ★★ same condition
- GORAB c.-28C>G Uncertain significance ★★ same condition
- GORAB p.Ala220Thr Uncertain significance ★★ same condition
- GORAB p.Ala31Thr Uncertain significance ★★ same condition
- GORAB p.Arg145His 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/gorab-p-pro86leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown