Is LYST p.Ser494= (c.1482G>A) pathogenic?

LYST p.Ser494= (c.1482G>A) is classified Likely benign in LYST (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). Ultra-rare (popmax 0.0505%, sas); Associated with Chediak-Higashi syndrome.

What condition is associated with LYST p.Ser494= (c.1482G>A)?

LYST p.Ser494= (c.1482G>A) is associated with Chediak-Higashi syndrome (ClinVar).

How common is LYST p.Ser494= (c.1482G>A) in the general population?

LYST p.Ser494= (c.1482G>A) is ultra-rare (popmax 0.0505%, sas) (gnomAD).

How is Chédiak-Higashi syndrome inherited?

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

LYST p.Ser494=

c.1482G>A · rs754596305 · VCV1629442

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0505%, sas)

Conditions

Chediak-Higashi syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2	GERP -4.6
Overall
CADD	4.886	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0505% South Asian · 46/91,062 alleles

Filtering AF 0.0389% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0348%

Overall 0.00403% 65/1,613,934 alleles · ultra-rare exomes 60/1,461,744 · genomes 5/152,190 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0505%	1,980
Middle Eastern	0.0165%	6,062
Admixed American	0.0133%	7,498
Remaining individualsnot grpmax-eligible	0.0032%	31,253
African / African-American	0.00133%	75,000
European (non-Finnish)	0.000593%	168,567

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.Ser494=
Coding: c.1482G>A
MANE Select: NM_000081
dbSNP: rs754596305
Type: single nucleotide variant
Location: chr1:235809336 (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.Ser494Leu Uncertain significance ★★ 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-ser494 (accessed [today's date]).

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