Is LYST p.Leu2926Val (c.8776C>G) pathogenic?

LYST p.Leu2926Val (c.8776C>G) is classified Uncertain significance in LYST (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). AlphaMissense: likely benign (0.0997); Very rare (popmax 0.00017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with LYST p.Leu2926Val (c.8776C>G)?

LYST p.Leu2926Val (c.8776C>G) is associated with Inborn genetic diseases (ClinVar).

How common is LYST p.Leu2926Val (c.8776C>G) in the general population?

LYST p.Leu2926Val (c.8776C>G) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about LYST p.Leu2926Val (c.8776C>G)?

AlphaMissense predicts likely benign (score 0.0997) — an in-silico prediction, not a clinical call.

LYST p.Leu2926Val

c.8776C>G · VCV4624059

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0997 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0997	likely benign
REVEL	0.21	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 8.5	GERP 2.4, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 71 kb · p 1.5e-17 · regional, not allelic
Overall
CADD	23.0	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

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,934 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,710 alleles · very rare

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.Leu2926Val
Coding: c.8776C>G
MANE Select: NM_000081
Type: single nucleotide variant
Location: chr1:235733528 (GRCh38)
Gene constraint: LOEUF 0.505 · pLI <0.01 (gnomAD)
Residue 2926: a UniProt-annotated variant site (in chs)

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

Similar variants

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LYST p.Ala2258Pro Uncertain significance ★★ ⚠ same condition
LYST p.Ala243Val Uncertain significance ★★ ⚠ same condition
LYST p.Ala2634Val Uncertain significance ★★ same condition
LYST p.Ala2758Thr Uncertain significance ★★ ⚠ same condition
LYST p.Ala2935Glu Uncertain significance ★★ ⚠ 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-leu2926val (accessed [today's date]).

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