Is RAB27A p.Pro158= (c.474C>T) pathogenic?

RAB27A p.Pro158= (c.474C>T) is classified Likely benign in RAB27A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-11). Ultra-rare (popmax 0.0164%, mid); Associated with Griscelli syndrome type 2.

What condition is associated with RAB27A p.Pro158= (c.474C>T)?

RAB27A p.Pro158= (c.474C>T) is associated with Griscelli syndrome type 2 (ClinVar).

How common is RAB27A p.Pro158= (c.474C>T) in the general population?

RAB27A p.Pro158= (c.474C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Familial hemophagocytic lymphohistiocytosis inherited?

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

RAB27A p.Pro158=

c.474C>T · rs777485094 · VCV1580439

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 0.65	GERP 0.36, phastCons 1
Overall
CADD	7.424	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00124% 20/1,613,256 alleles · ultra-rare exomes 16/1,461,120 · genomes 4/152,136 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Admixed American	0.00833%	12,000
South Asian	0.00329%	30,350
Remaining individualsnot grpmax-eligible	0.0032%	31,236
European (non-Finnish)	0.000763%	131,039

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.Pro158=
Coding: c.474C>T
MANE Select: NM_183235
dbSNP: rs777485094
Type: single nucleotide variant
Location: chr15:55205699 (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.Pro158Arg Uncertain significance ★★ ⚠ same residue
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

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-pro158 (accessed [today's date]).

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