Is GORAB p.Pro30= (c.90C>T) pathogenic?

GORAB p.Pro30= (c.90C>T) is classified Likely benign in GORAB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-13). Ultra-rare (popmax 0.0164%, mid).

How common is GORAB p.Pro30= (c.90C>T) in the general population?

GORAB p.Pro30= (c.90C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

GORAB p.Pro30=

c.90C>T · rs766244250 · VCV2167016

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2	GERP -3.1
Overall
CADD	2.799	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00136% 22/1,613,940 alleles · ultra-rare exomes 20/1,461,810 · genomes 2/152,130 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0064%	15,622
European (non-Finnish)	0.00136%	73,750
African / African-American	0.00134%	74,890

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.Pro30=
Coding: c.90C>T
MANE Select: NM_152281
dbSNP: rs766244250
Type: single nucleotide variant
Location: chr1:170539238 (GRCh38)
Gene constraint: LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.86
Residue 30: the 'disordered' region

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

Similar variants

GORAB p.Pro30Ala Uncertain significance ★★ same residue
GORAB p.Pro30His Uncertain significance ★★ same residue
GORAB p.Pro30Thr Uncertain significance ★ same residue
GORAB p.Pro30fs Likely pathogenic ★ same residue
GORAB p.Pro30_Ser57delinsGluValSerGly 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

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-pro30 (accessed [today's date]).

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