Is GORAB p.Arg27Ter (c.79C>T) pathogenic?

GORAB p.Arg27Ter (c.79C>T) is classified Pathogenic in GORAB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-10). Very rare (popmax 0.005%, amr).

How common is GORAB p.Arg27Ter (c.79C>T) in the general population?

GORAB p.Arg27Ter (c.79C>T) is very rare (popmax 0.005%, amr) (gnomAD).

GORAB p.Arg27Ter

c.79C>T · rs770355472 · VCV1360242

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 0.005%, amr)

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 2 of 5
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.8	GERP 1.7, phastCons 1
Overall
CADD	36.0	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 0.005% Admixed American · 3/59,978 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000929% 15/1,613,934 alleles · very rare exomes 12/1,461,794 · genomes 3/152,140 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,993
East Asian	0.00223%	44,892
European (non-Finnish)	0.000932%	107,271

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.Arg27Ter
Coding: c.79C>T
MANE Select: NM_152281
dbSNP: rs770355472
Type: single nucleotide variant
Location: chr1:170539227 (GRCh38)
Gene constraint: LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.86
Residue 27: the 'disordered' region

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

Similar variants

GORAB p.Arg27Gly Uncertain significance ★★ 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-arg27ter (accessed [today's date]).

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