GORAB p.Pro349Leu
c.1046C>T · rs145092592 · VCV1434367
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0658%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.094 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.74 | GERP 2.2 |
| Regional constraint | o/e 1.01 | unconstrained · MANE · 20 kb · p 0.84 · regional, not allelic |
| Overall | ||
| CADD | 15.41 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0658%
Middle Eastern · 4/6,082 alleles
Filtering AF
0.0224%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0135%
Overall
0.0031%
50/1,613,966 alleles · ultra-rare
exomes 39/1,461,788 · genomes 11/152,178 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0658% | 1,521 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,622 |
| European (non-Finnish) | 0.00331% | 30,256 |
| African / African-American | 0.00267% | 37,459 |
| Admixed American | 0.00167% | 59,998 |
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.Pro349Leu
- Coding
- c.1046C>T
- MANE Select
- NM_152281
- dbSNP
- rs145092592
- Type
- single nucleotide variant
- Location
- chr1:170552398 (GRCh38)
- Gene constraint
- LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 71.86
- Residue 349
- the 'necessary for interaction with rchy1' region; the 'disordered' region
Similar variants
- GORAB p.Pro349= Likely benign ★ same residue
- 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
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-pro349leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown