Is RAB44 p.Asp216Val (c.647A>T) pathogenic?

RAB44 p.Asp216Val (c.647A>T) is classified Uncertain significance in RAB44 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). AlphaMissense: ambiguous (0.3723); Ultra-rare (popmax 0.0718%, amr); Associated with familial meningioma.

What condition is associated with RAB44 p.Asp216Val (c.647A>T)?

RAB44 p.Asp216Val (c.647A>T) is associated with familial meningioma (ClinVar).

How common is RAB44 p.Asp216Val (c.647A>T) in the general population?

RAB44 p.Asp216Val (c.647A>T) is ultra-rare (popmax 0.0718%, amr) (gnomAD).

How is Meningioma inherited?

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

What do computational predictors say about RAB44 p.Asp216Val (c.647A>T)?

AlphaMissense predicts ambiguous (score 0.3723) — an in-silico prediction, not a clinical call.

RAB44 p.Asp216Val

c.647A>T · VCV3774538

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3723 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0718%, amr)

Conditions

familial meningioma

Computational evidence

Protein change
AlphaMissense	0.3723	ambiguous
SaProt	LLR -10.31	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.3	GERP 0.95, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 28 kb · p 2.6e-08 · regional, not allelic
Overall
CADD	16.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; SaProt is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0718% Admixed American · 17/23,674 alleles

Filtering AF 0.0457% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0375%

Overall 0.0359% 442/1,231,486 alleles · ultra-rare exomes 399/1,079,838 · genomes 43/151,648 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0718%	1,393
European (non-Finnish)	0.0409%	2,445
Remaining individualsnot grpmax-eligible	0.0372%	2,691
African / African-American	0.00623%	16,057

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.Asp216Val
Coding: c.647A>T
MANE Select: NM_001257357
Type: single nucleotide variant
Location: chr6:36718033 (GRCh38)
Gene constraint: LOEUF 1.029 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.25

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.Glu967Gln Uncertain significance ★ ⚠ same condition
RAB44 p.Pro393fs Uncertain significance ★ same condition
RAB44 p.Glu695= Likely benign ★ same type
RAB44 p.Ser778Pro Likely benign ★ 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/rab44-p-asp216val (accessed [today's date]).

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