Is GORAB p.Pro30Thr (c.88C>A) pathogenic?

GORAB p.Pro30Thr (c.88C>A) is classified Uncertain significance in GORAB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-03). Very rare (popmax 0.00133%, afr).

How common is GORAB p.Pro30Thr (c.88C>A) in the general population?

GORAB p.Pro30Thr (c.88C>A) is very rare (popmax 0.00133%, afr) (gnomAD).

GORAB p.Pro30Thr

c.88C>A · rs772771053 · VCV1913531

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.198	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 0.65, phastCons 0.055
Regional constraint	o/e 1.01	unconstrained · MANE · 20 kb · p 0.84 · regional, not allelic
Overall
CADD	11.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,920 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000682% 11/1,613,976 alleles · very rare exomes 10/1,461,816 · genomes 1/152,160 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,480
African / African-Americangrpmax	0.00133%	74,920
European (non-Finnish)	0.000763%	131,112

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro30Thr
Coding: c.88C>A
MANE Select: NM_152281
dbSNP: rs772771053
Type: single nucleotide variant
Location: chr1:170539236 (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.Pro30= Likely benign ★★ 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-pro30thr (accessed [today's date]).

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