Is LYST p.Asp2463= (c.7389T>C) pathogenic?

LYST p.Asp2463= (c.7389T>C) is classified Likely benign in LYST (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-03). Very rare (popmax 0.00366%, nfe); Associated with Chediak-Higashi syndrome.

What condition is associated with LYST p.Asp2463= (c.7389T>C)?

LYST p.Asp2463= (c.7389T>C) is associated with Chediak-Higashi syndrome (ClinVar).

How common is LYST p.Asp2463= (c.7389T>C) in the general population?

LYST p.Asp2463= (c.7389T>C) is very rare (popmax 0.00366%, nfe) (gnomAD).

How is Chédiak-Higashi syndrome inherited?

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

LYST p.Asp2463=

c.7389T>C · rs768399491 · VCV2042995

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00366%, 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 2.1	GERP -3.4, phastCons 1
Overall
CADD	8.029	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00366% European (non-Finnish) · 43/1,175,756 alleles

Filtering AF 0.00276% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00245%

Overall 0.00323% 52/1,609,014 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,383
European (non-Finnish)grpmax	0.00366%	27,343
Remaining individualsnot grpmax-eligible	0.00321%	31,150
African / African-American	0.00267%	37,401
Admixed American	0.00167%	59,972

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp2463=
Coding: c.7389T>C
MANE Select: NM_000081
dbSNP: rs768399491
Type: single nucleotide variant
Location: chr1:235753115 (GRCh38)
Gene constraint: LOEUF 0.505 · pLI <0.01 (gnomAD)
Residue 2463: 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-asp2463 (accessed [today's date]).

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