Is LAMP2 p.Arg293= (c.877C>A) pathogenic?

LAMP2 p.Arg293= (c.877C>A) is classified Benign/Likely benign in LAMP2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-22). Ultra-rare (popmax 0.0741%, sas); Associated with Cardiovascular phenotype.

What condition is associated with LAMP2 p.Arg293= (c.877C>A)?

LAMP2 p.Arg293= (c.877C>A) is associated with Cardiovascular phenotype, Danon disease (ClinVar).

How common is LAMP2 p.Arg293= (c.877C>A) in the general population?

LAMP2 p.Arg293= (c.877C>A) is ultra-rare (popmax 0.0741%, sas) (gnomAD).

LAMP2 p.Arg293=

c.877C>A · rs727503118 · VCV507194

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0741%, sas)

Conditions

Cardiovascular phenotype

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 · G>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.6	GERP 1.7, phastCons 1
Overall
CADD	10.36	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0741% South Asian · 42/56,718 alleles

Filtering AF 0.0562% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.05%

Overall 0.00398% 48/1,204,882 alleles · ultra-rare exomes 45/1,093,253 · genomes 3/111,629 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0741%	1,350
Remaining individualsnot grpmax-eligible	0.00843%	11,863
European (non-Finnish)	0.000224%	445,444

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.Arg293=
Coding: c.877C>A
MANE Select: NM_002294
dbSNP: rs727503118
Type: single nucleotide variant
Location: chrX:120442650 (GRCh38)
Structure: AlphaFold pLDDT 83.54 · 2 PDB
Residue 293: the 'second lumenal domain' region

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

Disease context

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

Also linked: Danon disease

Similar variants

LAMP2 p.Arg293Ter Pathogenic ★★ same residue
LAMP2 p.Arg293Gln 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

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-arg293 (accessed [today's date]).

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