Is LAMP2 p.Arg25Pro (c.74G>C) pathogenic?

LAMP2 p.Arg25Pro (c.74G>C) is classified Likely benign in LAMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-14). AlphaMissense: likely benign (0.0935); Very rare (popmax 0.0018%, afr); Associated with Cardiovascular phenotype.

What condition is associated with LAMP2 p.Arg25Pro (c.74G>C)?

LAMP2 p.Arg25Pro (c.74G>C) is associated with Cardiovascular phenotype (ClinVar).

How common is LAMP2 p.Arg25Pro (c.74G>C) in the general population?

LAMP2 p.Arg25Pro (c.74G>C) is very rare (popmax 0.0018%, afr) (gnomAD).

What do computational predictors say about LAMP2 p.Arg25Pro (c.74G>C)?

AlphaMissense predicts likely benign (score 0.0935) — an in-silico prediction, not a clinical call.

LAMP2 p.Arg25Pro

c.74G>C · rs750118236 · VCV3222067

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0935 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0018%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0935	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -4.89	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 -1.2	GERP -3.7
Regional constraint	o/e 0.90	unconstrained · MANE · 38 kb · p 0.09 · regional, not allelic
Overall
CADD	0.163	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 0.0018% African / African-American · 1/55,532 alleles

Overall 0.000101% 1/987,732 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.Arg25Pro
Coding: c.74G>C
MANE Select: NM_002294
dbSNP: rs750118236
Type: single nucleotide variant
Location: chrX:120456760 (GRCh38)
Structure: AlphaFold pLDDT 83.54 · 2 PDB

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

Similar variants

LAMP2 p.Arg25Trp Uncertain significance ★★ ⚠ same residue
LAMP2 p.Arg25Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
LAMP2 p.Arg25= Likely benign ★ same residue
LAMP2 c.183+1G>A Pathogenic/Likely pathogenic ★★ same condition
LAMP2 c.741+1G>A Pathogenic/Likely pathogenic ★★ same condition
LAMP2 p.Cys232Ter Pathogenic ★★ same condition
LAMP2 p.Gln359Ter Pathogenic/Likely pathogenic ★★ same condition
LAMP2 p.Met1Leu 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-arg25pro (accessed [today's date]).

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