Is LYST p.Asp2467Gly (c.7400A>G) pathogenic?

LYST p.Asp2467Gly (c.7400A>G) is classified Uncertain significance in LYST (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-24). AlphaMissense: likely pathogenic (0.7809); Rare (popmax 0.107%, eas); Associated with Chediak-Higashi syndrome.

What condition is associated with LYST p.Asp2467Gly (c.7400A>G)?

LYST p.Asp2467Gly (c.7400A>G) is associated with Chediak-Higashi syndrome (ClinVar).

How common is LYST p.Asp2467Gly (c.7400A>G) in the general population?

LYST p.Asp2467Gly (c.7400A>G) is rare (popmax 0.107%, eas) (gnomAD).

How is Chédiak-Higashi syndrome inherited?

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

What do computational predictors say about LYST p.Asp2467Gly (c.7400A>G)?

AlphaMissense predicts likely pathogenic (score 0.7809) — an in-silico prediction, not a clinical call.

LYST p.Asp2467Gly

c.7400A>G · VCV4807305

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7809 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.107%, eas)

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Chediak-Higashi syndrome

Computational evidence

Protein change
AlphaMissense	0.7809	likely pathogenic
REVEL	0.707	pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	Δ0.26	acceptor loss, 19 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 26 kb · p 0.022 · regional, not allelic
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.107% East Asian · 48/44,706 alleles

Filtering AF 0.0832% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0746%

Overall 0.00305% 49/1,608,880 alleles · rare exomes 47/1,456,660 · genomes 2/152,220 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.107%	931
Remaining individualsnot grpmax-eligible	0.00161%	62,294

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.Asp2467Gly
Coding: c.7400A>G
MANE Select: NM_000081
Type: single nucleotide variant
Location: chr1:235753104 (GRCh38)
Gene constraint: LOEUF 0.505 · pLI <0.01 (gnomAD)
Residue 2467: 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-asp2467gly (accessed [today's date]).

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