Is LYST p.Arg498= (c.1494A>G) pathogenic?

LYST p.Arg498= (c.1494A>G) is classified Benign/Likely benign in LYST (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-23). Rare (popmax 0.281%, eas); Associated with Chediak-Higashi syndrome.

What condition is associated with LYST p.Arg498= (c.1494A>G)?

LYST p.Arg498= (c.1494A>G) is associated with Chediak-Higashi syndrome (ClinVar).

How common is LYST p.Arg498= (c.1494A>G) in the general population?

LYST p.Arg498= (c.1494A>G) is rare (popmax 0.281%, eas) (gnomAD).

How is Chédiak-Higashi syndrome inherited?

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

LYST p.Arg498=

c.1494A>G · rs201412615 · VCV296430

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.281%, eas)

Conditions

Chediak-Higashi 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 -1.9	GERP -4.1
Overall
CADD	1.598	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.281% East Asian · 126/44,882 alleles

Filtering AF 0.241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.226%

Overall 0.00905% 146/1,614,110 alleles · rare exomes 131/1,461,788 · genomes 15/152,322 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.281%	356
Remaining individualsnot grpmax-eligible	0.0144%	6,945
South Asian	0.00988%	10,120
Admixed American	0.00167%	60,008
European (non-Finnish)	8.47e-05%	1,179,986

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: LYST
Protein: p.Arg498=
Coding: c.1494A>G
MANE Select: NM_000081
dbSNP: rs201412615
Type: single nucleotide variant
Location: chr1:235809324 (GRCh38)
Gene constraint: LOEUF 0.505 · pLI <0.01 (gnomAD)

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

Disease context

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

For Chédiak-Higashi syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

LYST p.Arg498Ter Pathogenic ★ same residue
LYST c.192+1G>A Pathogenic/Likely pathogenic ★★ same condition
LYST c.4862+2T>A Likely pathogenic ★★ same condition
LYST c.4863-1G>C Likely pathogenic ★★ same condition
LYST c.6882-1G>T Likely pathogenic ★★ same condition
LYST c.8358+2T>C Pathogenic/Likely pathogenic ★★ same condition
LYST c.8358+2T>G Likely pathogenic ★★ same condition
LYST c.8802-2A>G 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/lyst-p-arg498 (accessed [today's date]).

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