Is LAMP2 p.Asp372= (c.1116C>T) pathogenic?

LAMP2 p.Asp372= (c.1116C>T) is classified Likely benign in LAMP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-09). Very rare (popmax 0.00296%, eas); Associated with Danon disease.

What condition is associated with LAMP2 p.Asp372= (c.1116C>T)?

LAMP2 p.Asp372= (c.1116C>T) is associated with Danon disease (ClinVar).

How common is LAMP2 p.Asp372= (c.1116C>T) in the general population?

LAMP2 p.Asp372= (c.1116C>T) is very rare (popmax 0.00296%, eas) (gnomAD).

How is Danon disease inherited?

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

LAMP2 p.Asp372=

c.1116C>T · rs749338632 · VCV792992

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

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 0.97	GERP -3.4, phastCons 1
Overall
CADD	5.155	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00296% East Asian · 1/33,798 alleles

Filtering AF 8.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.000579% 7/1,208,512 alleles · very rare exomes 5/1,096,162 · genomes 2/112,350 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00421%	23,757
East Asiangrpmax	0.00296%	33,798
African / African-American	0.00174%	57,320
European (non-Finnish)	0.000336%	297,865

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp372=
Coding: c.1116C>T
MANE Select: NM_002294
dbSNP: rs749338632
Type: single nucleotide variant
Location: chrX:120431440 (GRCh38)
Structure: AlphaFold pLDDT 83.54 · 2 PDB
Residue 372: the 'second 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.Asp372Glu Uncertain significance ★ ⚠ 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-asp372 (accessed [today's date]).

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