Is RAB33B p.Arg32= (c.96C>G) pathogenic?

RAB33B p.Arg32= (c.96C>G) is classified Likely benign in RAB33B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-09). Ultra-rare (popmax 0.04%, afr).

How common is RAB33B p.Arg32= (c.96C>G) in the general population?

RAB33B p.Arg32= (c.96C>G) is ultra-rare (popmax 0.04%, afr) (gnomAD).

RAB33B p.Arg32=

c.96C>G · rs147523243 · VCV752500

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.04%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.53	GERP 0.97, phastCons 1
Overall
CADD	12.78	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.04% African / African-American · 30/74,918 alleles

Filtering AF 0.0288% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0249%

Overall 0.00192% 31/1,614,062 alleles · ultra-rare exomes 14/1,461,874 · genomes 17/152,188 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.04%	2,497
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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: RAB33B
Protein: p.Arg32=
Coding: c.96C>G
MANE Select: NM_031296
dbSNP: rs147523243
Type: single nucleotide variant
Location: chr4:139454291 (GRCh38)
Gene constraint: LOEUF 0.774 · pLI 0.39 (gnomAD)
Structure: AlphaFold pLDDT 81.55 · 2 PDB
Residue 32: a β-strand

Full RAB33B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RAB33B p.Arg32Cys Uncertain significance ★ ⚠ same residue
RAB33B p.Gln134Ter Pathogenic ★★ same type
RAB33B c.*2355T>A Uncertain significance ★★ same type
RAB33B p.Asn139Lys Uncertain significance ★★ ⚠ same type
RAB33B p.Asn185Asp Uncertain significance ★★ ⚠ same type
RAB33B p.Asn43Ser Uncertain significance ★★ ⚠ same type
RAB33B p.Ile191Met Uncertain significance ★★ ⚠ same type
RAB33B p.Ile33Leu Uncertain significance ★★ 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/rab33b-p-arg32 (accessed [today's date]).

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