Is LYST p.Phe701= (c.2103T>C) pathogenic?

LYST p.Phe701= (c.2103T>C) is classified Likely benign in LYST (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-23). Very rare (popmax 0.004%, afr); Associated with Chediak-Higashi syndrome.

What condition is associated with LYST p.Phe701= (c.2103T>C)?

LYST p.Phe701= (c.2103T>C) is associated with Chediak-Higashi syndrome (ClinVar).

How common is LYST p.Phe701= (c.2103T>C) in the general population?

LYST p.Phe701= (c.2103T>C) is very rare (popmax 0.004%, afr) (gnomAD).

How is Chédiak-Higashi syndrome inherited?

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

LYST p.Phe701=

c.2103T>C · rs1304503707 · VCV1105271

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

Chediak-Higashi syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.93	GERP 0.96, phastCons 0.98
Overall
CADD	7.183	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,934 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,613,928 alleles · very rare exomes 3/1,461,700 · genomes 1/152,228 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,978
Remaining individualsnot grpmax-eligible	0.0016%	62,478

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.Phe701=
Coding: c.2103T>C
MANE Select: NM_000081
dbSNP: rs1304503707
Type: single nucleotide variant
Location: chr1:235808715 (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 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-phe701 (accessed [today's date]).

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