Is RAB23 p.Ala84= (c.252T>G) pathogenic?

RAB23 p.Ala84= (c.252T>G) is classified Likely benign in RAB23 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-01-24). Very rare (popmax 0.00167%, amr); Associated with RAB23-related disorder.

What condition is associated with RAB23 p.Ala84= (c.252T>G)?

RAB23 p.Ala84= (c.252T>G) is associated with RAB23-related disorder (ClinVar).

How common is RAB23 p.Ala84= (c.252T>G) in the general population?

RAB23 p.Ala84= (c.252T>G) is very rare (popmax 0.00167%, amr) (gnomAD).

RAB23 p.Ala84=

c.252T>G · rs1346414063 · VCV3057917

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

RAB23-related disorder

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 2.4	GERP -2.2, phastCons 1
Overall
CADD	9.753	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,988 alleles

Overall 6.2e-05% 1/1,613,842 alleles · very rare exomes 1/1,461,520 · genomes 0/152,322 · 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: RAB23
Protein: p.Ala84=
Coding: c.252T>G
MANE Select: NM_016277
dbSNP: rs1346414063
Type: single nucleotide variant
Location: chr6:57196596 (GRCh38)
Gene constraint: LOEUF 0.838 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 80.39 · 6 PDB
Residue 84: a β-strand

Full RAB23 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

RAB23-related disorder

Similar variants

RAB23 p.Leu145Ter Pathogenic ★★ same condition
RAB23 p.Cys30Trp Uncertain significance ★★ ⚠ same condition
RAB23 c.575-10A>G Uncertain significance same condition
RAB23 p.Arg218Thr Uncertain significance ⚠ same condition
RAB23 p.Asp5Glu Uncertain significance ⚠ same condition
RAB23 p.Gln222Lys Uncertain significance ⚠ same condition
RAB23 p.Gly112Val Uncertain significance ⚠ same condition
RAB23 p.Gly203Asp 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/rab23-p-ala84 (accessed [today's date]).

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