GORAB p.Phe23=
c.69T>C · rs374051444 · VCV3013753
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0103%, nfe)
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 2 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 7.413 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0103%
European (non-Finnish) · 121/1,180,018 alleles
Filtering AF
0.00876%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0082%
Overall
0.00762%
123/1,614,040 alleles · ultra-rare
exomes 119/1,461,816 · genomes 4/152,224 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0103% | 9,752 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,244 |
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.Phe23=
- Coding
- c.69T>C
- MANE Select
- NM_152281
- dbSNP
- rs374051444
- Type
- single nucleotide variant
- Location
- chr1:170539217 (GRCh38)
- Gene constraint
- LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 71.86
- Residue 23
- the 'disordered' region
Similar variants
- GORAB c.420-2A>T Pathogenic/Likely pathogenic ★★ same type
- GORAB p.Arg262Ter Pathogenic/Likely pathogenic ★★ same type
- GORAB p.Arg35Ter Pathogenic ★★ same type
- GORAB p.Arg40Ter Pathogenic/Likely pathogenic ★★ same type
- GORAB p.Gln64Ter Pathogenic ★★ same type
- GORAB p.Trp5Ter Pathogenic/Likely pathogenic ★★ same type
- GORAB c.-21G>A Uncertain significance ★★ same type
- GORAB c.-28C>G 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/gorab-p-phe23 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown