Is LAMP2 p.Ser155= (c.465T>C) pathogenic?

LAMP2 p.Ser155= (c.465T>C) is classified Likely benign in LAMP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-16). Very rare (popmax 0.000225%, nfe); Associated with Danon disease.

What condition is associated with LAMP2 p.Ser155= (c.465T>C)?

LAMP2 p.Ser155= (c.465T>C) is associated with Danon disease (ClinVar).

How common is LAMP2 p.Ser155= (c.465T>C) in the general population?

LAMP2 p.Ser155= (c.465T>C) is very rare (popmax 0.000225%, nfe) (gnomAD).

How is Danon disease inherited?

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

LAMP2 p.Ser155=

c.465T>C · rs2520888495 · VCV2723325

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000225%, nfe)

Conditions

Danon disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.39 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.2	GERP 0.8, phastCons 0.88
Overall
CADD	12.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000225% European (non-Finnish) · 2/887,124 alleles

Filtering AF 3.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000166% 2/1,202,808 alleles · very rare exomes 2/1,088,734 · genomes 0/114,074 · 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: LAMP2
Protein: p.Ser155=
Coding: c.465T>C
MANE Select: NM_002294
dbSNP: rs2520888495
Type: single nucleotide variant
Location: chrX:120449061 (GRCh38)
Structure: AlphaFold pLDDT 83.54 · 2 PDB
Residue 155: 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.Ser155Gly Uncertain significance ★ ⚠ same residue
LAMP2 p.Ser155fs Likely pathogenic ★★ 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

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-ser155 (accessed [today's date]).

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