Is LYST p.Ser239Ile (c.716G>T) pathogenic?

LYST p.Ser239Ile (c.716G>T) is classified Uncertain significance in LYST (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-01). AlphaMissense: likely benign (0.2291); Absent from gnomAD v4.1; Associated with Chediak-Higashi syndrome.

What condition is associated with LYST p.Ser239Ile (c.716G>T)?

LYST p.Ser239Ile (c.716G>T) is associated with Chediak-Higashi syndrome (ClinVar).

How common is LYST p.Ser239Ile (c.716G>T) in the general population?

LYST p.Ser239Ile (c.716G>T) is absent from gnomAD v4.1 (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.Ser239Ile (c.716G>T)?

AlphaMissense predicts likely benign (score 0.2291) — an in-silico prediction, not a clinical call.

LYST p.Ser239Ile

c.716G>T · rs534142793 · VCV2012894

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2291 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Chediak-Higashi syndrome

Computational evidence

Protein change
AlphaMissense	0.2291	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 42 kb · p 0.00014 · regional, not allelic
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LYST
Protein: p.Ser239Ile
Coding: c.716G>T
MANE Select: NM_000081
dbSNP: rs534142793
Type: single nucleotide variant
Location: chr1:235810102 (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.Ser239= Likely benign ★★ same residue
LYST p.Ser239Asn 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

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-ser239ile (accessed [today's date]).

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