Is LPIN2 p.Pro378= (c.1134G>A) pathogenic?

LPIN2 p.Pro378= (c.1134G>A) is classified Conflicting classifications of pathogenicity in LPIN2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-02-01). Rare (popmax 0.135%, sas); Associated with autoinflammatory syndrome.

What condition is associated with LPIN2 p.Pro378= (c.1134G>A)?

LPIN2 p.Pro378= (c.1134G>A) is associated with autoinflammatory syndrome, Majeed syndrome (ClinVar).

How common is LPIN2 p.Pro378= (c.1134G>A) in the general population?

LPIN2 p.Pro378= (c.1134G>A) is rare (popmax 0.135%, sas) (gnomAD).

LPIN2 p.Pro378=

c.1134G>A · rs543890845 · VCV1694292

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.135%, sas)

Conditions

autoinflammatory syndrome

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 0.055	GERP 0.59, phastCons 0.005
Overall
CADD	8.555	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.135% South Asian · 123/91,076 alleles

Filtering AF 0.116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.108%

Overall 0.00855% 138/1,614,000 alleles · rare exomes 124/1,461,868 · genomes 14/152,132 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.135%	740
Remaining individualsnot grpmax-eligible	0.0112%	8,930
African / African-American	0.008%	12,496
Finnishnot grpmax-eligible	0.00156%	63,962
European (non-Finnish)	8.47e-05%	1,180,018

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: LPIN2
Protein: p.Pro378=
Coding: c.1134G>A
MANE Select: NM_001375808
dbSNP: rs543890845
Type: single nucleotide variant
Location: chr18:2937726 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 61.12
Residue 378: the 'disordered' region

Full LPIN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autoinflammatory syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Majeed syndrome

Similar variants

LPIN2 p.Pro378Leu Uncertain significance ★★ ⚠ same residue
LPIN2 p.Pro378Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
LPIN2 c.1269-2A>G Likely pathogenic ★★ same condition
LPIN2 c.698+1G>A Likely pathogenic ★★ same condition
LPIN2 c.699-2A>G Likely pathogenic ★★ same condition
LPIN2 p.Arg157Ter Pathogenic ★★ same condition
LPIN2 p.Arg197Ter Pathogenic/Likely pathogenic ★★ same condition
LPIN2 p.Arg280Ter 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/lpin2-p-pro378 (accessed [today's date]).

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