Is LYST p.Arg207Cys (c.619C>T) pathogenic?

LYST p.Arg207Cys (c.619C>T) is classified Uncertain significance in LYST (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-06). AlphaMissense: likely benign (0.0694); Ultra-rare (popmax 0.0164%, mid); Associated with Chediak-Higashi syndrome.

What condition is associated with LYST p.Arg207Cys (c.619C>T)?

LYST p.Arg207Cys (c.619C>T) is associated with Chediak-Higashi syndrome (ClinVar).

How common is LYST p.Arg207Cys (c.619C>T) in the general population?

LYST p.Arg207Cys (c.619C>T) is ultra-rare (popmax 0.0164%, mid) (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.Arg207Cys (c.619C>T)?

AlphaMissense predicts likely benign (score 0.0694) — an in-silico prediction, not a clinical call.

LYST p.Arg207Cys

c.619C>T · rs748789807 · VCV1970557

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0694 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Chediak-Higashi syndrome

Computational evidence

Protein change
AlphaMissense	0.0694	likely benign
REVEL	0.074	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 0.63	GERP 0.2
Regional constraint	o/e 0.91	unconstrained · MANE · 42 kb · p 0.00014 · regional, not allelic
Overall
CADD	15.72	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

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00155% 25/1,613,902 alleles · ultra-rare exomes 24/1,461,782 · genomes 1/152,120 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.00267%	37,443
East Asian	0.00223%	44,898
European (non-Finnish)	0.00169%	58,998
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Arg207Cys
Coding: c.619C>T
MANE Select: NM_000081
dbSNP: rs748789807
Type: single nucleotide variant
Location: chr1:235810199 (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.Arg207His Uncertain significance ★ ⚠ same residue
LYST p.Arg207= Likely benign ★ 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-arg207cys (accessed [today's date]).

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