Is LYST p.Pro883Ala (c.2647C>G) pathogenic?

LYST p.Pro883Ala (c.2647C>G) is classified Conflicting classifications of pathogenicity in LYST (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-02-16). AlphaMissense: likely benign (0.1256); Ultra-rare (popmax 0.0535%, eas); Associated with Inborn genetic diseases.

What condition is associated with LYST p.Pro883Ala (c.2647C>G)?

LYST p.Pro883Ala (c.2647C>G) is associated with Inborn genetic diseases, Chediak-Higashi syndrome (ClinVar).

How common is LYST p.Pro883Ala (c.2647C>G) in the general population?

LYST p.Pro883Ala (c.2647C>G) is ultra-rare (popmax 0.0535%, eas) (gnomAD).

What do computational predictors say about LYST p.Pro883Ala (c.2647C>G)?

AlphaMissense predicts likely benign (score 0.1256) — an in-silico prediction, not a clinical call.

LYST p.Pro883Ala

c.2647C>G · rs180889778 · VCV945578

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1256 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0535%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1256	likely benign
REVEL	0.238	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 5.9	GERP 1.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 42 kb · p 0.00014 · regional, not allelic
Overall
CADD	19.83	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0535% East Asian · 24/44,872 alleles

Filtering AF 0.0368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0313%

Overall 0.00149% 24/1,614,040 alleles · ultra-rare exomes 20/1,461,810 · genomes 4/152,230 · joint denominator

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.Pro883Ala
Coding: c.2647C>G
MANE Select: NM_000081
dbSNP: rs180889778
Type: single nucleotide variant
Location: chr1:235806489 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Chediak-Higashi syndrome

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-pro883ala (accessed [today's date]).

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