Is LYST p.Ser671del (c.2009CTT[1]) pathogenic?

LYST p.Ser671del (c.2009CTT[1]) is classified Uncertain significance in LYST (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-14). Rare (popmax 0.164%, sas); Associated with Chediak-Higashi syndrome.

What condition is associated with LYST p.Ser671del (c.2009CTT[1])?

LYST p.Ser671del (c.2009CTT[1]) is associated with Chediak-Higashi syndrome (ClinVar).

How common is LYST p.Ser671del (c.2009CTT[1]) in the general population?

LYST p.Ser671del (c.2009CTT[1]) is rare (popmax 0.164%, sas) (gnomAD).

How is Chédiak-Higashi syndrome inherited?

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

LYST p.Ser671del

c.2009CTT[1] · rs552601776 · VCV296425

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.164%, sas)

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 · substitutions only
Constraint at this position
Conservation	phyloP 0.15	GERP -1.5
Overall
CADD	7.611	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.164% South Asian · 149/91,090 alleles

Filtering AF 0.142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.134%

Overall 0.00985% 159/1,614,068 alleles · rare exomes 151/1,461,746 · genomes 8/152,322 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.164%	611
African / African-American	0.00666%	15,010
Remaining individualsnot grpmax-eligible	0.0048%	20,836
European (non-Finnish)	0.000169%	589,998

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.Ser671del
Coding: c.2009CTT[1]
MANE Select: NM_000081
dbSNP: rs552601776
Type: Microsatellite
Location: chr1:235808804 (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.Ser671= Likely benign ★ same residue
LYST p.Asp792fs Likely pathogenic ★★ same condition
LYST p.Glu1441fs Pathogenic ★★ same condition
LYST p.Glu1203del Uncertain significance ★★ same condition
LYST p.Glu1219del Uncertain significance ★★ same condition
LYST p.Val2266del Uncertain significance ★★ same condition
LYST c.7229+50CTTTT[7] Benign ★★ same condition
LYST c.7461-11_7461-9del 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-ser671del (accessed [today's date]).

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