GORAB p.Ala314Val
c.941C>T · rs187680628 · VCV293662
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.11%, amr)
Conditions
1
geroderma osteodysplasticum
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.151 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.24 | GERP -0.65 |
| Regional constraint | o/e 1.01 | unconstrained · MANE · 20 kb · p 0.84 · regional, not allelic |
| Overall | ||
| CADD | 13.19 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.11%
Admixed American · 66/59,998 alleles
Filtering AF
0.0887%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0809%
Overall
0.0111%
179/1,614,014 alleles · rare
exomes 142/1,461,824 · genomes 37/152,190 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.11% | 909 |
| South Asian | 0.0692% | 1,446 |
| East Asian | 0.0178% | 5,610 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,813 |
| African / African-American | 0.00667% | 15,000 |
| European (non-Finnish) | 0.00246% | 40,689 |
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.Ala314Val
- Coding
- c.941C>T
- MANE Select
- NM_152281
- dbSNP
- rs187680628
- Type
- single nucleotide variant
- Location
- chr1:170552293 (GRCh38)
- Gene constraint
- LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 71.86
- Residue 314
- the 'necessary for interaction with rchy1' region
Similar variants
- GORAB p.Ala314= Likely benign ★★ same residue
- GORAB p.Ala314Gly Uncertain significance ★ same residue
- 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
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-ala314val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown