Is GORAB p.Pro356Ser (c.1066C>T) pathogenic?

GORAB p.Pro356Ser (c.1066C>T) is classified Uncertain significance in GORAB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-11). Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with GORAB p.Pro356Ser (c.1066C>T)?

GORAB p.Pro356Ser (c.1066C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GORAB p.Pro356Ser (c.1066C>T) in the general population?

GORAB p.Pro356Ser (c.1066C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

GORAB p.Pro356Ser

c.1066C>T · VCV3521323

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.02	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.39	GERP -3.1
Regional constraint	o/e 1.01	unconstrained · MANE · 20 kb · p 0.84 · regional, not allelic
Overall
CADD	5.471	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,882 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000124% 2/1,613,976 alleles · very rare exomes 2/1,461,744 · genomes 0/152,232 · 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.Pro356Ser
Coding: c.1066C>T
MANE Select: NM_152281
Type: single nucleotide variant
Location: chr1:170552418 (GRCh38)
Gene constraint: LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.86
Residue 356: the 'necessary for interaction with rchy1' region; the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GORAB p.Pro356= Likely benign ★ same residue
GORAB p.Arg35Ter Pathogenic ★★ same condition
GORAB c.-21G>A Uncertain significance ★★ same condition
GORAB c.-28C>G Uncertain significance ★★ same condition
GORAB p.Ala220Thr Uncertain significance ★★ same condition
GORAB p.Ala31Thr Uncertain significance ★★ same condition
GORAB p.Arg145His Uncertain significance ★★ same condition
GORAB p.Arg187Trp Uncertain significance ★★ same condition

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-pro356ser (accessed [today's date]).

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