Is GORAB p.Gln3Ter (c.7C>T) pathogenic?

GORAB p.Gln3Ter (c.7C>T) is classified Pathogenic in GORAB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-16). Very rare (popmax 8.47e-05%, nfe).

How common is GORAB p.Gln3Ter (c.7C>T) in the general population?

GORAB p.Gln3Ter (c.7C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

GORAB p.Gln3Ter

c.7C>T · rs2525903868 · VCV2766333

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 5
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.1	GERP -0.42, phastCons 1
Overall
CADD	37.0	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 8.47e-05% European (non-Finnish) · 1/1,179,994 alleles

Overall 6.2e-05% 1/1,613,998 alleles · very rare exomes 1/1,461,812 · genomes 0/152,186 · joint denominator

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.Gln3Ter
Coding: c.7C>T
MANE Select: NM_152281
dbSNP: rs2525903868
Type: single nucleotide variant
Location: chr1:170532230 (GRCh38)
Gene constraint: LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.86
Residue 3: the 'disordered' region

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

Similar variants

GORAB p.Gln3= 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-gln3ter (accessed [today's date]).

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