Is LAMP2 p.Phe397= (c.1191T>C) pathogenic?

LAMP2 p.Phe397= (c.1191T>C) is classified Benign/Likely benign in LAMP2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-05-25). Ultra-rare (popmax 0.0317%, sas); Associated with Danon disease.

What condition is associated with LAMP2 p.Phe397= (c.1191T>C)?

LAMP2 p.Phe397= (c.1191T>C) is associated with Danon disease (ClinVar).

How common is LAMP2 p.Phe397= (c.1191T>C) in the general population?

LAMP2 p.Phe397= (c.1191T>C) is ultra-rare (popmax 0.0317%, sas) (gnomAD).

How is Danon disease inherited?

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

LAMP2 p.Phe397=

c.1191T>C · rs752231323 · VCV381155

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0317%, sas)

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 5.9	GERP -0.7, phastCons 1
Overall
CADD	10.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0317% South Asian · 18/56,834 alleles

Filtering AF 0.0204% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0168%

Overall 0.00637% 77/1,208,941 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0317%	3,157
European (non-Finnish)	0.00626%	15,964
Remaining individualsnot grpmax-eligible	0.00421%	23,773
Admixed American	0.00218%	45,787

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.Phe397=
Coding: c.1191T>C
MANE Select: NM_002294
dbSNP: rs752231323
Type: single nucleotide variant
Location: chrX:120431365 (GRCh38)
Structure: AlphaFold pLDDT 83.54 · 2 PDB
Residue 397: an α-helix

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-phe397 (accessed [today's date]).

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