Is LAMP2 p.Pro324Ser (c.970C>T) pathogenic?

LAMP2 p.Pro324Ser (c.970C>T) is classified Conflicting classifications of pathogenicity in LAMP2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-06-22). AlphaMissense: likely benign (0.2147); Very rare (popmax 0.00235%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with LAMP2 p.Pro324Ser (c.970C>T)?

LAMP2 p.Pro324Ser (c.970C>T) is associated with Cardiovascular phenotype, Danon disease (ClinVar).

How common is LAMP2 p.Pro324Ser (c.970C>T) in the general population?

LAMP2 p.Pro324Ser (c.970C>T) is very rare (popmax 0.00235%, nfe) (gnomAD).

What do computational predictors say about LAMP2 p.Pro324Ser (c.970C>T)?

AlphaMissense predicts likely benign (score 0.2147) — an in-silico prediction, not a clinical call.

LAMP2 p.Pro324Ser

c.970C>T · rs866736614 · VCV1503237

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2147 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00235%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.2147	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -8.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 0.23, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 38 kb · p 0.09 · regional, not allelic
Overall
CADD	19.18	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00235% European (non-Finnish) · 21/894,026 alleles

Filtering AF 0.00151% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00128%

Overall 0.00191% 21/1,096,616 alleles · very rare

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.Pro324Ser
Coding: c.970C>T
MANE Select: NM_002294
dbSNP: rs866736614
Type: single nucleotide variant
Location: chrX:120441853 (GRCh38)
Structure: AlphaFold pLDDT 83.54 · 2 PDB
Residue 324: 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.Pro324= Likely benign ★★ 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-pro324ser (accessed [today's date]).

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