Is RAB18 p.Pro35Ser (c.103C>T) pathogenic?

RAB18 p.Pro35Ser (c.103C>T) is classified Uncertain significance in RAB18 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-19). AlphaMissense: likely benign (0.3055); Absent from gnomAD v4.1; Associated with Warburg micro syndrome 3.

What condition is associated with RAB18 p.Pro35Ser (c.103C>T)?

RAB18 p.Pro35Ser (c.103C>T) is associated with Warburg micro syndrome 3 (ClinVar).

How common is RAB18 p.Pro35Ser (c.103C>T) in the general population?

RAB18 p.Pro35Ser (c.103C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RAB18 p.Pro35Ser (c.103C>T)?

AlphaMissense predicts likely benign (score 0.3055) — an in-silico prediction, not a clinical call.

RAB18 p.Pro35Ser

c.103C>T · rs2491605143 · VCV2435348

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3055 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Warburg micro syndrome 3

Computational evidence

Protein change
AlphaMissense	0.3055	likely benign
REVEL	0.334	indeterminate
SaProt	LLR -7.84	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 34 kb · p 0.00032 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RAB18
Protein: p.Pro35Ser
Coding: c.103C>T
MANE Select: NM_021252
dbSNP: rs2491605143
Type: single nucleotide variant
Location: chr10:27509909 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 86.10 · 1 PDB
Residue 35: a binding site

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 p.Pro35Leu Uncertain significance ★ same residue
RAB18 p.Pro35= Likely benign ★ same residue
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

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-pro35ser (accessed [today's date]).

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