Is LAMP2 p.Val197= (c.591G>A) pathogenic?

LAMP2 p.Val197= (c.591G>A) is classified Benign/Likely benign in LAMP2 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-01-24). Rare (popmax 0.46%, mid); Associated with Cardiovascular phenotype.

What condition is associated with LAMP2 p.Val197= (c.591G>A)?

LAMP2 p.Val197= (c.591G>A) is associated with Cardiovascular phenotype, Danon disease (ClinVar).

How common is LAMP2 p.Val197= (c.591G>A) in the general population?

LAMP2 p.Val197= (c.591G>A) is rare (popmax 0.46%, mid) (gnomAD).

LAMP2 p.Val197=

c.591G>A · rs201030806 · VCV44433

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Rare

rare (popmax 0.46%, mid)

Conditions

Cardiovascular phenotype

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 -0.54	GERP -4
Overall
CADD	1.368	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.46% Middle Eastern · 20/4,348 alleles

Filtering AF 0.305% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.255%

Overall 0.0213% 258/1,208,543 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.46%	217
Ashkenazi Jewishnot grpmax-eligible	0.15%	667
Remaining individualsnot grpmax-eligible	0.0504%	1,983
South Asian	0.0282%	3,548
European (non-Finnish)	0.0175%	5,698
Admixed American	0.0132%	7,600
African / African-American	0.00352%	28,407

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.Val197=
Coding: c.591G>A
MANE Select: NM_002294
dbSNP: rs201030806
Type: single nucleotide variant
Location: chrX:120447991 (GRCh38)
Structure: AlphaFold pLDDT 83.54 · 2 PDB
Residue 197: the 'hinge' 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.Val197Leu Uncertain significance ★ ⚠ same residue
LAMP2 p.Val197Met Uncertain significance ★ ⚠ same residue
LAMP2 p.Val197fs 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

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-val197 (accessed [today's date]).

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