Is LYST p.Pro588fs (c.1758_1761dup) pathogenic?

LYST p.Pro588fs (c.17581761dup) is classified Pathogenic in LYST (ClinVar, Single submitter, 2 submitters; last evaluated 2023-07-31). Absent from gnomAD; Associated with Chediak-Higashi syndrome.

What condition is associated with LYST p.Pro588fs (c.1758_1761dup)?

LYST p.Pro588fs (c.1758_1761dup) is associated with Chediak-Higashi syndrome (ClinVar).

How common is LYST p.Pro588fs (c.1758_1761dup) in the general population?

LYST p.Pro588fs (c.1758_1761dup) is absent from gnomAD (gnomAD).

How is Chédiak-Higashi syndrome inherited?

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

LYST p.Pro588fs

c.1758_1761dup · rs2527110492 · VCV2748630

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Chediak-Higashi syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 53
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: LYST
Protein: p.Pro588fs
Coding: c.1758_1761dup
MANE Select: NM_000081
dbSNP: rs2527110492
Type: Duplication
Location: chr1:235809056 (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.Glu2809fs Pathogenic/Likely pathogenic ★★ same condition
LYST p.Leu2379fs Pathogenic/Likely pathogenic ★★ same condition
LYST p.Leu3082fs Pathogenic/Likely pathogenic ★★ same condition
LYST p.Tyr2026Ter Pathogenic ★★ same condition
LYST p.Tyr3628Ter Pathogenic/Likely pathogenic ★★ same condition
LYST p.Tyr672Ter Pathogenic ★★ same condition
LYST c.11268-17dup Benign/Likely benign ★★ same condition
LYST c.2363+10dup Likely benign ★★ 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-pro588fs (accessed [today's date]).

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