Is LYST p.Asp772= (c.2316C>T) pathogenic?

LYST p.Asp772= (c.2316C>T) is classified Benign/Likely benign in LYST (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 19%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Chediak-Higashi syndrome.

What condition is associated with LYST p.Asp772= (c.2316C>T)?

LYST p.Asp772= (c.2316C>T) is associated with Chediak-Higashi syndrome (ClinVar).

How is Chédiak-Higashi syndrome inherited?

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

LYST p.Asp772=

Q: How common is LYST p.Asp772= (c.2316C>T) in the general population?

LYST p.Asp772= (c.2316C>T) is common (popmax 19%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2316C>T · rs16832868 · VCV254914

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 19%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.001	GERP -1.3, phastCons 0.94
Overall
CADD	14.58	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 19% African / African-American · 14,194/74,728 alleles

Filtering AF 18.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 18.6%

Overall 1.03% 16,588/1,613,264 alleles · common exomes 8,333/1,461,634 · genomes 8,255/151,630 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	19%	5
Remaining individualsnot grpmax-eligible	1.38%	72
Admixed American	1.3%	77
Middle Eastern	1.07%	93
Ashkenazi Jewishnot grpmax-eligible	0.206%	485
European (non-Finnish)	0.0498%	2,010
South Asian	0.0417%	2,396

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.Asp772=
Coding: c.2316C>T
MANE Select: NM_000081
dbSNP: rs16832868
Type: single nucleotide variant
Location: chr1:235808502 (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.Asp772Glu Conflicting classifications of pathogenicity ★ ⚠ 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-asp772 (accessed [today's date]).

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