Is RAB27A p.Val199= (c.597G>A) pathogenic?

RAB27A p.Val199= (c.597G>A) is classified Likely benign in RAB27A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-28). Very rare (popmax 0.0011%, sas); Associated with Griscelli syndrome type 2.

What condition is associated with RAB27A p.Val199= (c.597G>A)?

RAB27A p.Val199= (c.597G>A) is associated with Griscelli syndrome type 2 (ClinVar).

How common is RAB27A p.Val199= (c.597G>A) in the general population?

RAB27A p.Val199= (c.597G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Familial hemophagocytic lymphohistiocytosis inherited?

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

RAB27A p.Val199=

c.597G>A · rs1894604106 · VCV1664964

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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
Pangolin	Δ0.32	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -0.077	GERP -0.2, phastCons 0.54
Overall
CADD	6.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,084 alleles

Overall 0.000137% 2/1,461,840 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,084
European (non-Finnish)	8.47e-05%	1,179,997

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.Val199=
Coding: c.597G>A
MANE Select: NM_183235
dbSNP: rs1894604106
Type: single nucleotide variant
Location: chr15:55205576 (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.Val199Ala Uncertain significance ★ ⚠ same residue
RAB27A p.Val199Glu 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

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-val199 (accessed [today's date]).

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