GORAB p.Glu290Lys
c.868G>A · rs541180988 · VCV1391742
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00534%, afr)
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.247 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 8.7 | GERP 1.8, phastCons 1 |
| Regional constraint | o/e 1.01 | unconstrained · MANE · 20 kb · p 0.84 · regional, not allelic |
| Overall | ||
| CADD | 22.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00534%
African / African-American · 4/74,922 alleles
Filtering AF
0.00315%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00279%
Overall
0.00328%
53/1,613,998 alleles · very rare
exomes 47/1,461,818 · genomes 6/152,180 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00534% | 18,730 |
| European (non-Finnish) | 0.00407% | 24,583 |
| Finnishnot grpmax-eligible | 0.00156% | 64,024 |
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.Glu290Lys
- Coding
- c.868G>A
- MANE Select
- NM_152281
- dbSNP
- rs541180988
- Type
- single nucleotide variant
- Location
- chr1:170552220 (GRCh38)
- Gene constraint
- LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 71.86
- Residue 290
- the 'necessary for interaction with rchy1' region
Similar variants
- GORAB p.Arg262Ter Pathogenic/Likely pathogenic ★★ same condition
- GORAB p.Arg35Ter Pathogenic ★★ same condition
- GORAB p.Arg40Ter Pathogenic/Likely pathogenic ★★ same condition
- GORAB p.Gln64Ter Pathogenic ★★ same condition
- GORAB c.-21G>A Uncertain significance ★★ same condition
- GORAB c.-28C>G Uncertain significance ★★ same condition
- GORAB c.-53C>A Uncertain significance ★★ same condition
- GORAB p.Ala220Thr 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-glu290lys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown