Is RAB18 p.Val131= (c.393C>T) pathogenic?

RAB18 p.Val131= (c.393C>T) is classified Likely benign in RAB18 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-05-08). Very rare (popmax 0.00167%, amr); Associated with RAB18-related disorder.

What condition is associated with RAB18 p.Val131= (c.393C>T)?

RAB18 p.Val131= (c.393C>T) is associated with RAB18-related disorder (ClinVar).

How common is RAB18 p.Val131= (c.393C>T) in the general population?

RAB18 p.Val131= (c.393C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

RAB18 p.Val131=

c.393C>T · rs769837798 · VCV3029842

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

RAB18-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -4.3	GERP -3.2
Overall
CADD	4.647	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,980 alleles

Filtering AF 0.000544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00043%

Overall 0.000932% 15/1,609,876 alleles · very rare exomes 13/1,457,842 · genomes 2/152,034 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,980
African / African-American	0.00134%	74,754
South Asian	0.0011%	90,970
European (non-Finnish)	0.00102%	98,044

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.Val131=
Coding: c.393C>T
MANE Select: NM_021252
dbSNP: rs769837798
Type: single nucleotide variant
Location: chr10:27533942 (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

RAB18-related disorder

Similar variants

RAB18 c.379-2A>G Uncertain significance same condition
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
RAB18 p.Thr32Met 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-val131 (accessed [today's date]).

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