Is LYST p.Asp95= (c.285T>C) pathogenic?

LYST p.Asp95= (c.285T>C) is classified Conflicting classifications of pathogenicity in LYST (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-21). Very rare (popmax 0.00834%, amr); Associated with Chediak-Higashi syndrome.

What condition is associated with LYST p.Asp95= (c.285T>C)?

LYST p.Asp95= (c.285T>C) is associated with Chediak-Higashi syndrome (ClinVar).

How common is LYST p.Asp95= (c.285T>C) in the general population?

LYST p.Asp95= (c.285T>C) is very rare (popmax 0.00834%, amr) (gnomAD).

How is Chédiak-Higashi syndrome inherited?

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

LYST p.Asp95=

c.285T>C · rs747965676 · VCV1088059

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

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 4.1	GERP -0.38, phastCons 1
Overall
CADD	10.05	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00834% Admixed American · 5/59,974 alleles

Filtering AF 0.00511% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00509% 82/1,609,924 alleles · very rare exomes 73/1,457,724 · genomes 9/152,200 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00834%	11,995
European (non-Finnish)	0.00627%	15,941
Remaining individualsnot grpmax-eligible	0.00481%	20,809

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.Asp95=
Coding: c.285T>C
MANE Select: NM_000081
dbSNP: rs747965676
Type: single nucleotide variant
Location: chr1:235810533 (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.Asp95Glu 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-asp95 (accessed [today's date]).

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