Is GORAB p.Ser93fs (c.276del) pathogenic?

GORAB p.Ser93fs (c.276del) is classified Pathogenic in GORAB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-02). Very rare (popmax 8.47e-05%, nfe).

How common is GORAB p.Ser93fs (c.276del) in the general population?

GORAB p.Ser93fs (c.276del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

GORAB p.Ser93fs

c.276del · rs1558004538 · VCV1355774

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

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	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.61	GERP -1.4

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) · 1/1,179,990 alleles

Overall 6.2e-05% 1/1,614,012 alleles · very rare exomes 1/1,461,850 · genomes 0/152,162 · 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.Ser93fs
Coding: c.276del
MANE Select: NM_152281
dbSNP: rs1558004538
Type: Deletion
Location: chr1:170539423 (GRCh38)
Gene constraint: LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.86
Residue 93: the 'disordered' region

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

Similar variants

GORAB p.Ser93= Likely benign ★★ same residue
GORAB p.Ala2fs Pathogenic/Likely pathogenic ★★ same type
GORAB p.Lys137fs Pathogenic/Likely pathogenic ★★ same type
GORAB p.Pro86fs Pathogenic/Likely pathogenic ★★ same type
GORAB p.Ser335fs Uncertain significance ★★ same type
GORAB c.420-20del Likely benign ★★ same type
GORAB p.Arg187fs Pathogenic ★ same type
GORAB p.Asn74fs Pathogenic ★ 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-ser93fs (accessed [today's date]).

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