Is RAB27A p.Val198= (c.594G>A) pathogenic?

RAB27A p.Val198= (c.594G>A) is classified Benign/Likely benign in RAB27A (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-06-01). Low-frequency (popmax 1.2%, afr); Associated with autoinflammatory syndrome.

What condition is associated with RAB27A p.Val198= (c.594G>A)?

RAB27A p.Val198= (c.594G>A) is associated with autoinflammatory syndrome, Griscelli syndrome type 2 (ClinVar).

How common is RAB27A p.Val198= (c.594G>A) in the general population?

RAB27A p.Val198= (c.594G>A) is low-frequency (popmax 1.2%, afr) (gnomAD).

RAB27A p.Val198=

c.594G>A · rs141222527 · VCV468591

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.2%, afr)

Conditions

autoinflammatory syndrome

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 0.16	GERP 3, phastCons 0.95
Overall
CADD	8.062	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.2% African / African-American · 897/75,044 alleles

Filtering AF 1.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1%

Overall 0.0633% 1,021/1,614,132 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.2%	84
Admixed American	0.105%	953
Remaining individualsnot grpmax-eligible	0.0768%	1,302
Middle Eastern	0.0495%	2,020
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
South Asian	0.0011%	91,078
European (non-Finnish)	0.000678%	147,498

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.Val198=
Coding: c.594G>A
MANE Select: NM_183235
dbSNP: rs141222527
Type: single nucleotide variant
Location: chr15:55205579 (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

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

Also linked: Griscelli syndrome type 2

Similar variants

RAB27A p.Val198Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
RAB27A p.Val198Leu Uncertain significance ★ ⚠ same residue
RAB27A p.Val198Met 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

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-val198 (accessed [today's date]).

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