Is GORAB p.Ala31Val (c.92C>T) pathogenic?

GORAB p.Ala31Val (c.92C>T) is classified Conflicting classifications of pathogenicity in GORAB (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2022-08-16). Ultra-rare (popmax 0.0693%, afr); Associated with Inborn genetic diseases.

What condition is associated with GORAB p.Ala31Val (c.92C>T)?

GORAB p.Ala31Val (c.92C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GORAB p.Ala31Val (c.92C>T) in the general population?

GORAB p.Ala31Val (c.92C>T) is ultra-rare (popmax 0.0693%, afr) (gnomAD).

GORAB p.Ala31Val

c.92C>T · rs138420081 · VCV1524665

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0693%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.054	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.3	GERP -2.4, phastCons 0.008
Regional constraint	o/e 1.01	unconstrained · MANE · 20 kb · p 0.84 · regional, not allelic
Overall
CADD	0.279	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0693% African / African-American · 52/75,024 alleles

Filtering AF 0.0542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0489%

Overall 0.00527% 85/1,614,084 alleles · ultra-rare exomes 55/1,461,812 · genomes 30/152,272 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0693%	1,443
Middle Eastern	0.0165%	6,062
Admixed American	0.01%	9,999
Remaining individualsnot grpmax-eligible	0.0064%	15,627
South Asian	0.0022%	45,539
European (non-Finnish)	0.00169%	59,000

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.Ala31Val
Coding: c.92C>T
MANE Select: NM_152281
dbSNP: rs138420081
Type: single nucleotide variant
Location: chr1:170539240 (GRCh38)
Gene constraint: LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.86
Residue 31: the 'disordered' region

Full GORAB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GORAB p.Ala31Thr Uncertain significance ★★ same residue
GORAB p.Ala31= Likely benign ★ same residue
GORAB p.Arg35Ter Pathogenic ★★ same condition
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.Arg145His Uncertain significance ★★ same condition
GORAB p.Arg187Trp 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-ala31val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown