Is LYST p.Ile2829= (c.8487C>T) pathogenic?

LYST p.Ile2829= (c.8487C>T) is classified Conflicting classifications of pathogenicity in LYST (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-04-01). Rare (popmax 0.206%, nfe); Associated with Chediak-Higashi syndrome.

What condition is associated with LYST p.Ile2829= (c.8487C>T)?

LYST p.Ile2829= (c.8487C>T) is associated with Chediak-Higashi syndrome (ClinVar).

How common is LYST p.Ile2829= (c.8487C>T) in the general population?

LYST p.Ile2829= (c.8487C>T) is rare (popmax 0.206%, nfe) (gnomAD).

How is Chédiak-Higashi syndrome inherited?

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

LYST p.Ile2829=

c.8487C>T · rs144597913 · VCV522322

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.206%, nfe)

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 0.75	GERP -3.4, phastCons 0.38
Overall
CADD	4.696	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.206% European (non-Finnish) · 2,435/1,179,620 alleles

Filtering AF 0.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.197%

Overall 0.166% 2,671/1,613,634 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.206%	484
Remaining individualsnot grpmax-eligible	0.114%	880
South Asian	0.0933%	1,071
Middle Eastern	0.0825%	1,212
Ashkenazi Jewishnot grpmax-eligible	0.0507%	1,973
Finnishnot grpmax-eligible	0.0453%	2,208
Admixed American	0.0233%	4,286
African / African-American	0.0227%	4,413

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.Ile2829=
Coding: c.8487C>T
MANE Select: NM_000081
dbSNP: rs144597913
Type: single nucleotide variant
Location: chr1:235734531 (GRCh38)
Gene constraint: LOEUF 0.505 · pLI <0.01 (gnomAD)
Residue 2829: a UniProt-annotated variant site (in chs)

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 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
LYST c.9784+1G>T 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-ile2829 (accessed [today's date]).

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