Is GORAB p.Pro62Gln (c.185C>A) pathogenic?

GORAB p.Pro62Gln (c.185C>A) is classified Uncertain significance in GORAB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-12). Very rare (popmax 0.004%, afr); Associated with Inborn genetic diseases.

What condition is associated with GORAB p.Pro62Gln (c.185C>A)?

GORAB p.Pro62Gln (c.185C>A) is associated with Inborn genetic diseases (ClinVar).

How common is GORAB p.Pro62Gln (c.185C>A) in the general population?

GORAB p.Pro62Gln (c.185C>A) is very rare (popmax 0.004%, afr) (gnomAD).

GORAB p.Pro62Gln

c.185C>A · VCV3521322

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.199	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 0.7, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 20 kb · p 0.84 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,920 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,614,032 alleles · very rare exomes 2/1,461,870 · genomes 1/152,162 · 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.Pro62Gln
Coding: c.185C>A
MANE Select: NM_152281
Type: single nucleotide variant
Location: chr1:170539333 (GRCh38)
Gene constraint: LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.86
Residue 62: 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.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
GORAB p.Arg209Gln 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-pro62gln (accessed [today's date]).

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