Is RAB27A c.154del pathogenic?

RAB27A c.154del is classified Likely pathogenic in RAB27A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-20). Very rare (popmax 8.49e-05%, nfe); Associated with Griscelli syndrome type 2.

What condition is associated with RAB27A c.154del?

RAB27A c.154del is associated with Griscelli syndrome type 2 (ClinVar).

How common is RAB27A c.154del in the general population?

RAB27A c.154del is very rare (popmax 8.49e-05%, nfe) (gnomAD).

How is Familial hemophagocytic lymphohistiocytosis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

RAB27A c.154del

VCV3341467

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Conditions

Griscelli syndrome type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 7.4, phastCons 1
Non-coding constraint	Z 1.14	1 kb window · o/e 0.91 · regional · uncalibrated

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,178,406 alleles

Overall 6.85e-05% 1/1,459,878 alleles · very rare

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: RAB27A
Coding: c.154del
MANE Select: NM_183235
Type: Deletion
Location: chr15:55230486 (GRCh38)
Gene constraint: LOEUF 1.126 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 84.69 · 11 PDB

Full RAB27A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Griscelli syndrome type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial hemophagocytic lymphohistiocytosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Infancy
Prevalence: 1-9 / 100 000 (Sweden)

Similar variants

RAB27A p.Asn112fs Pathogenic ★★ same condition
RAB27A p.Gln172fs Pathogenic ★★ same condition
RAB27A p.Lys134fs Pathogenic/Likely pathogenic ★★ same condition
RAB27A p.Pro126fs Pathogenic ★★ same condition
RAB27A p.Tyr6_Asp7delinsTer Pathogenic ★★ same condition
RAB27A c.240-5_242del Pathogenic ★ same condition
RAB27A c.467+3_467+6del Pathogenic ★ same condition
RAB27A p.Ala148fs Pathogenic ★ 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/rab27a-c-154del (accessed [today's date]).

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