Is LIPA p.Pro370= (c.1110G>A) pathogenic?

LIPA p.Pro370= (c.1110G>A) is classified Likely benign in LIPA (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-03-24). Very rare (popmax 0.00439%, sas); Associated with Cardiovascular phenotype.

What condition is associated with LIPA p.Pro370= (c.1110G>A)?

LIPA p.Pro370= (c.1110G>A) is associated with Cardiovascular phenotype, Wolman disease, lysosomal acid lipase deficiency (ClinVar).

How common is LIPA p.Pro370= (c.1110G>A) in the general population?

LIPA p.Pro370= (c.1110G>A) is very rare (popmax 0.00439%, sas) (gnomAD).

LIPA p.Pro370=

c.1110G>A · rs1381270290 · VCV1091073

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

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 -6.8	GERP -3.9
Overall
CADD	0.348	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,080 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00186% 30/1,613,876 alleles · very rare exomes 26/1,461,756 · genomes 4/152,120 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,770
Remaining individualsnot grpmax-eligible	0.0032%	31,239
African / African-American	0.00267%	37,450
European (non-Finnish)	0.00186%	53,633

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: LIPA
Protein: p.Pro370=
Coding: c.1110G>A
MANE Select: NM_000235
dbSNP: rs1381270290
Type: single nucleotide variant
Location: chr10:89214918 (GRCh38)
Structure: AlphaFold pLDDT 89.74

Full LIPA 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: Wolman disease lysosomal acid lipase deficiency

Similar variants

LIPA p.Pro370Ala Uncertain significance ★★ ⚠ same residue
LIPA p.Pro370Leu Uncertain significance ★ ⚠ same residue
LIPA c.111+1G>A Pathogenic/Likely pathogenic ★★ same condition
LIPA c.539-2A>G Pathogenic ★★ same condition
LIPA c.675+2T>G Likely pathogenic ★★ same condition
LIPA c.676-2A>T Pathogenic ★★ same condition
LIPA c.822+1G>A Likely pathogenic ★★ same condition
LIPA c.823-2A>G 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/lipa-p-pro370 (accessed [today's date]).

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