Is RAB27A p.Ala55= (c.165C>T) pathogenic?

RAB27A p.Ala55= (c.165C>T) is classified Likely benign in RAB27A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-07). Ultra-rare (popmax 0.0401%, eas); Associated with Griscelli syndrome type 2.

What condition is associated with RAB27A p.Ala55= (c.165C>T)?

RAB27A p.Ala55= (c.165C>T) is associated with Griscelli syndrome type 2 (ClinVar).

How common is RAB27A p.Ala55= (c.165C>T) in the general population?

RAB27A p.Ala55= (c.165C>T) is ultra-rare (popmax 0.0401%, eas) (gnomAD).

How is Familial hemophagocytic lymphohistiocytosis inherited?

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

RAB27A p.Ala55=

c.165C>T · rs765203586 · VCV1135895

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0401%, eas)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 3.9, phastCons 1
Overall
CADD	9.137	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0401% East Asian · 18/44,866 alleles

Filtering AF 0.0259% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0214%

Overall 0.00149% 24/1,613,124 alleles · ultra-rare exomes 22/1,461,036 · genomes 2/152,088 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0401%	2,493
African / African-American	0.00401%	24,955
Remaining individualsnot grpmax-eligible	0.0016%	62,456
South Asian	0.0011%	91,064
European (non-Finnish)	8.48e-05%	1,179,414

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
Protein: p.Ala55=
Coding: c.165C>T
MANE Select: NM_183235
dbSNP: rs765203586
Type: single nucleotide variant
Location: chr15:55230475 (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 c.239+1G>T Pathogenic ★★ same condition
RAB27A c.467+1G>C Pathogenic/Likely pathogenic ★★ same condition
RAB27A p.Ala76Val Pathogenic/Likely pathogenic ★★ same condition
RAB27A p.Arg184Ter Pathogenic ★★ same condition
RAB27A p.Arg82Cys Pathogenic/Likely pathogenic ★★ same condition
RAB27A p.Asp74His Likely pathogenic ★★ same condition
RAB27A p.Gln118Ter Pathogenic ★★ same condition
RAB27A p.Gln172Ter Pathogenic/Likely 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-p-ala55 (accessed [today's date]).

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