Is LAMP2 p.Ala129= (c.387T>C) pathogenic?

LAMP2 p.Ala129= (c.387T>C) is classified Likely benign in LAMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-30). Absent from gnomAD v4.1; Associated with Danon disease.

What condition is associated with LAMP2 p.Ala129= (c.387T>C)?

LAMP2 p.Ala129= (c.387T>C) is associated with Danon disease (ClinVar).

How common is LAMP2 p.Ala129= (c.387T>C) in the general population?

LAMP2 p.Ala129= (c.387T>C) is absent from gnomAD v4.1 (gnomAD).

How is Danon disease inherited?

Typically X-linked dominant (Orphanet). A genetic counselor can assess individual risk for a family.

LAMP2 p.Ala129=

c.387T>C · rs2520906827 · VCV2970111

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Danon disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.36	GERP -3.8
Overall
CADD	8.163	PHRED · no single calibrated threshold — expert panels disagree

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: LAMP2
Protein: p.Ala129=
Coding: c.387T>C
MANE Select: NM_002294
dbSNP: rs2520906827
Type: single nucleotide variant
Location: chrX:120455367 (GRCh38)
Structure: AlphaFold pLDDT 83.54 · 2 PDB
Residue 129: the 'first lumenal domain' region

Full LAMP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Danon disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Danon disease (Orphanet):

Inheritance: X-linked dominant
Onset: Childhood

Similar variants

LAMP2 p.Ala129Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
LAMP2 c.1093+1G>A Pathogenic ★★ same condition
LAMP2 c.183+1G>A Pathogenic/Likely pathogenic ★★ same condition
LAMP2 c.183+2T>C Pathogenic ★★ same condition
LAMP2 c.65-1G>C Pathogenic/Likely pathogenic ★★ same condition
LAMP2 c.65-2A>G Pathogenic ★★ same condition
LAMP2 c.741+1G>A Pathogenic/Likely pathogenic ★★ same condition
LAMP2 c.864+1G>A 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/lamp2-p-ala129 (accessed [today's date]).

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