Is GORAB p.Trp5Ter (c.14G>A) pathogenic?

GORAB p.Trp5Ter (c.14G>A) is classified Pathogenic/Likely pathogenic in GORAB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-23). Very rare (popmax 0.00167%, amr).

How common is GORAB p.Trp5Ter (c.14G>A) in the general population?

GORAB p.Trp5Ter (c.14G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

GORAB p.Trp5Ter

c.14G>A · rs761242807 · VCV2832462

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 5
Splicing
SpliceAI	Δ0.34	donor gain · deltas
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Overall
CADD	45.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,012 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,614,022 alleles · very rare exomes 5/1,461,832 · genomes 1/152,190 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,012
European (non-Finnish)	0.000424%	236,007

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.Trp5Ter
Coding: c.14G>A
MANE Select: NM_152281
dbSNP: rs761242807
Type: single nucleotide variant
Location: chr1:170532237 (GRCh38)
Gene constraint: LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.86
Residue 5: the 'disordered' region

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

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 c.-21G>A Uncertain significance ★★ same type
GORAB c.-28C>G Uncertain significance ★★ same type
GORAB c.-53C>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-trp5ter (accessed [today's date]).

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