Is LIPA p.Pro285Ser (c.853C>T) pathogenic?

LIPA p.Pro285Ser (c.853C>T) is classified Uncertain significance in LIPA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-31). AlphaMissense: likely pathogenic (0.7348); Very rare (popmax 8.5e-05%, nfe); Associated with Wolman disease.

What condition is associated with LIPA p.Pro285Ser (c.853C>T)?

LIPA p.Pro285Ser (c.853C>T) is associated with Wolman disease (ClinVar).

How common is LIPA p.Pro285Ser (c.853C>T) in the general population?

LIPA p.Pro285Ser (c.853C>T) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

How is Lysosomal acid lipase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about LIPA p.Pro285Ser (c.853C>T)?

AlphaMissense predicts likely pathogenic (score 0.7348) — an in-silico prediction, not a clinical call.

LIPA p.Pro285Ser

c.853C>T · rs1564752079 · VCV577668

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7348 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Wolman disease

Computational evidence

Protein change
AlphaMissense	0.7348	likely pathogenic · top 2% in LIPA
REVEL	0.498	indeterminate
SaProt	LLR -8.73	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 1.9, phastCons 1
Overall
CADD	27.2	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 8.5e-05% European (non-Finnish) · 1/1,176,104 alleles

Overall 6.21e-05% 1/1,609,830 alleles · very rare exomes 1/1,457,536 · genomes 0/152,294 · joint denominator

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.Pro285Ser
Coding: c.853C>T
MANE Select: NM_000235
dbSNP: rs1564752079
Type: single nucleotide variant
Location: chr10:89222552 (GRCh38)
Structure: AlphaFold pLDDT 89.74

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

Disease context

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

For Lysosomal acid lipase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Czech Republic)

Similar variants

LIPA p.Pro285fs Pathogenic ★ same residue
LIPA p.Pro285= Likely benign ★ 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-pro285ser (accessed [today's date]).

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