Is LAMP2 p.Phe151= (c.453T>C) pathogenic?

LAMP2 p.Phe151= (c.453T>C) is classified Likely benign in LAMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-29). Ultra-rare (popmax 0.0118%, eas); Associated with Danon disease.

What condition is associated with LAMP2 p.Phe151= (c.453T>C)?

LAMP2 p.Phe151= (c.453T>C) is associated with Danon disease (ClinVar).

How common is LAMP2 p.Phe151= (c.453T>C) in the general population?

LAMP2 p.Phe151= (c.453T>C) is ultra-rare (popmax 0.0118%, eas) (gnomAD).

How is Danon disease inherited?

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

LAMP2 p.Phe151=

c.453T>C · rs200348335 · VCV765823

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0118%, eas)

Conditions

Danon disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.29	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 2.1	GERP -0.45, phastCons 1
Overall
CADD	15.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0118% East Asian · 4/33,769 alleles

Filtering AF 0.00396% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.000416% 5/1,202,291 alleles · ultra-rare exomes 4/1,089,636 · genomes 1/112,655 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0118%	8,442
European (non-Finnish)	0.000113%	887,784

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.Phe151=
Coding: c.453T>C
MANE Select: NM_002294
dbSNP: rs200348335
Type: single nucleotide variant
Location: chrX:120449073 (GRCh38)
Structure: AlphaFold pLDDT 83.54 · 2 PDB
Residue 151: 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 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
LAMP2 c.864+1G>T 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-phe151 (accessed [today's date]).

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