Is LAMP2 p.Ser309= (c.927C>T) pathogenic?

LAMP2 p.Ser309= (c.927C>T) is classified Benign/Likely benign in LAMP2 (ClinVar, Multiple submitters, 18 submitters; last evaluated 2026-02-04). Low-frequency (popmax 4.42%, mid); Associated with Cardiovascular phenotype.

What condition is associated with LAMP2 p.Ser309= (c.927C>T)?

LAMP2 p.Ser309= (c.927C>T) is associated with Cardiovascular phenotype, hypertrophic cardiomyopathy, Danon disease (ClinVar).

How common is LAMP2 p.Ser309= (c.927C>T) in the general population?

LAMP2 p.Ser309= (c.927C>T) is low-frequency (popmax 4.42%, mid) (gnomAD).

LAMP2 p.Ser309=

c.927C>T · rs73219144 · VCV44445

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 18 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.42%, 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 2.3	GERP -2.8, phastCons 1
Overall
CADD	5.384	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.42% Middle Eastern · 192/4,344 alleles

Filtering AF 3.93% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.92%

Overall 3.42% 41,101/1,203,141 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	4.42%	23
European (non-Finnish)	3.96%	25
Finnishnot grpmax-eligible	3.93%	25
Remaining individualsnot grpmax-eligible	3.24%	31
Ashkenazi Jewishnot grpmax-eligible	3.02%	33
Amishnot grpmax-eligible	2.19%	46
Admixed American	1.84%	54
South Asian	0.918%	109
African / African-American	0.454%	221
East Asian	0.00593%	16,868

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.Ser309=
Coding: c.927C>T
MANE Select: NM_002294
dbSNP: rs73219144
Type: single nucleotide variant
Location: chrX:120442600 (GRCh38)
Structure: AlphaFold pLDDT 83.54 · 2 PDB
Residue 309: 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: hypertrophic cardiomyopathy Danon disease

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-ser309 (accessed [today's date]).

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