Is RAB44 p.Pro393fs (c.1178del) pathogenic?

RAB44 p.Pro393fs (c.1178del) is classified Uncertain significance in RAB44 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). Rare (popmax 0.136%, nfe); Associated with familial meningioma.

What condition is associated with RAB44 p.Pro393fs (c.1178del)?

RAB44 p.Pro393fs (c.1178del) is associated with familial meningioma (ClinVar).

How common is RAB44 p.Pro393fs (c.1178del) in the general population?

RAB44 p.Pro393fs (c.1178del) is rare (popmax 0.136%, nfe) (gnomAD).

How is Meningioma inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

RAB44 p.Pro393fs

c.1178del · VCV3774537

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.136%, nfe)

Conditions

familial meningioma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -8.7	GERP -2.6
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.136% European (non-Finnish) · 1,341/987,784 alleles

Filtering AF 0.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.127%

Overall 0.116% 1,429/1,233,466 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.136%	737
Remaining individualsnot grpmax-eligible	0.0892%	1,121
South Asian	0.0533%	1,875
Finnishnot grpmax-eligible	0.053%	1,887
Admixed American	0.0254%	3,945
African / African-American	0.0155%	6,433
East Asian	0.00316%	31,656

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: RAB44
Protein: p.Pro393fs
Coding: c.1178del
MANE Select: NM_001257357
Type: Deletion
Location: chr6:36721308 (GRCh38)
Gene constraint: LOEUF 1.029 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.25
Residue 393: the 'disordered' region

Full RAB44 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial meningioma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Meningioma (Orphanet):

Inheritance: Not applicable
Onset: All ages
Prevalence: 1-9 / 100 000 (Germany)

Similar variants

RAB44 p.Asp216Val Uncertain significance ★ same condition
RAB44 p.Glu967Gln 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/rab44-p-pro393fs (accessed [today's date]).

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