Is RAB18 p.Val90= (c.270C>A) pathogenic?

RAB18 p.Val90= (c.270C>A) is classified Uncertain significance in RAB18 (ClinVar, Single submitter, 2 submitters; last evaluated 2018-01-13). Ultra-rare (popmax 0.0462%, sas); Associated with Warburg micro syndrome 3.

What condition is associated with RAB18 p.Val90= (c.270C>A)?

RAB18 p.Val90= (c.270C>A) is associated with Warburg micro syndrome 3 (ClinVar).

How common is RAB18 p.Val90= (c.270C>A) in the general population?

RAB18 p.Val90= (c.270C>A) is ultra-rare (popmax 0.0462%, sas) (gnomAD).

RAB18 p.Val90=

c.270C>A · rs750139202 · VCV299817

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0462%, sas)

Conditions

Warburg micro syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.069	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.28	GERP -2.2, phastCons 0.98
Overall
CADD	6.886	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0462% South Asian · 42/90,970 alleles

Filtering AF 0.0351% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0312%

Overall 0.00267% 43/1,613,002 alleles · ultra-rare exomes 42/1,460,984 · genomes 1/152,018 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0462%	2,166
Remaining individualsnot grpmax-eligible	0.0016%	62,450

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: RAB18
Protein: p.Val90=
Coding: c.270C>A
MANE Select: NM_021252
dbSNP: rs750139202
Type: single nucleotide variant
Location: chr10:27533745 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 86.10 · 1 PDB

Full RAB18 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Warburg micro syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RAB18 c.*4008C>T Uncertain significance ★★ same condition
RAB18 c.*402T>C Uncertain significance ★★ same condition
RAB18 p.Asp132Tyr Uncertain significance ★★ ⚠ same condition
RAB18 p.Ile61Met Uncertain significance ★★ ⚠ same condition
RAB18 c.-20C>T Benign/Likely benign ★★ same condition
RAB18 c.-83C>A Benign/Likely benign ★★ same condition
RAB18 c.*1542T>C Benign ★★ same condition
RAB18 c.*2375A>G Benign ★★ 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/rab18-p-val90 (accessed [today's date]).

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