Is GORAB p.Arg154Trp (c.460C>T) pathogenic?

GORAB p.Arg154Trp (c.460C>T) is classified Uncertain significance in GORAB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-10). Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with GORAB p.Arg154Trp (c.460C>T)?

GORAB p.Arg154Trp (c.460C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GORAB p.Arg154Trp (c.460C>T) in the general population?

GORAB p.Arg154Trp (c.460C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

GORAB p.Arg154Trp

c.460C>T · rs764714028 · VCV2475394

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.275	benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.3	GERP 0.38, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 20 kb · p 0.84 · regional, not allelic
Overall
CADD	29.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,824 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000496% 8/1,613,616 alleles · very rare exomes 8/1,461,424 · genomes 0/152,192 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,824
Admixed American	0.00167%	60,006
Finnishnot grpmax-eligible	0.00156%	63,970
African / African-American	0.00133%	74,992
European (non-Finnish)	0.000339%	294,928

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.Arg154Trp
Coding: c.460C>T
MANE Select: NM_152281
dbSNP: rs764714028
Type: single nucleotide variant
Location: chr1:170542531 (GRCh38)
Gene constraint: LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.86

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.Arg154Gln Uncertain significance ★★ 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.Ala31Thr 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-arg154trp (accessed [today's date]).

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