Is RAB18 p.Pro35= (c.105A>G) pathogenic?

RAB18 p.Pro35= (c.105A>G) is classified Likely benign in RAB18 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-10). Very rare (popmax 0.00549%, sas).

How common is RAB18 p.Pro35= (c.105A>G) in the general population?

RAB18 p.Pro35= (c.105A>G) is very rare (popmax 0.00549%, sas) (gnomAD).

RAB18 p.Pro35=

c.105A>G · rs144242088 · VCV2147852

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.032	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.51	GERP -3.8, phastCons 0.82
Overall
CADD	10.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,054 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00236% 38/1,612,654 alleles · very rare exomes 35/1,460,430 · genomes 3/152,224 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,211
Admixed American	0.00333%	30,002
Remaining individualsnot grpmax-eligible	0.0032%	31,235
European (non-Finnish)	0.00246%	40,654

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.Pro35=
Coding: c.105A>G
MANE Select: NM_021252
dbSNP: rs144242088
Type: single nucleotide variant
Location: chr10:27509911 (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

Similar variants

RAB18 p.Pro35Leu Uncertain significance ★ same residue
RAB18 p.Pro35Ser Uncertain significance ★ ⚠ same residue
RAB18 c.*4008C>T Uncertain significance ★★ same type
RAB18 c.*402T>C Uncertain significance ★★ same type
RAB18 p.Asp132Tyr Uncertain significance ★★ ⚠ same type
RAB18 p.Gly136Ser Uncertain significance ★★ ⚠ same type
RAB18 p.Ile61Met Uncertain significance ★★ ⚠ same type
RAB18 p.Ser151Asn 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/rab18-p-pro35 (accessed [today's date]).

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