Is LIPA p.Ser297= (c.891C>T) pathogenic?

LIPA p.Ser297= (c.891C>T) is classified Conflicting classifications of pathogenicity in LIPA (ClinVar, Conflicting submitters, 11 submitters; last evaluated 2026-02-02). Ultra-rare (popmax 0.0754%, nfe); Associated with lysosomal acid lipase deficiency.

What condition is associated with LIPA p.Ser297= (c.891C>T)?

LIPA p.Ser297= (c.891C>T) is associated with lysosomal acid lipase deficiency, Wolman disease, cholesteryl ester storage disease (ClinVar).

How common is LIPA p.Ser297= (c.891C>T) in the general population?

LIPA p.Ser297= (c.891C>T) is ultra-rare (popmax 0.0754%, nfe) (gnomAD).

How is Lysosomal acid lipase deficiency inherited?

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

LIPA p.Ser297=

c.891C>T · rs145066614 · VCV301575

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0754%, nfe)

Conditions

lysosomal acid lipase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.023	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.82	GERP -3.6
Overall
CADD	4.483	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0754% European (non-Finnish) · 882/1,170,524 alleles

Filtering AF 0.0712% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0695%

Overall 0.0587% 941/1,603,646 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0754%	1,327
Admixed American	0.04%	2,500
Remaining individualsnot grpmax-eligible	0.0386%	2,588
African / African-American	0.0147%	6,799

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.Ser297=
Coding: c.891C>T
MANE Select: NM_006552 · reported on NM_000235
dbSNP: rs145066614
Type: single nucleotide variant
Location: chr10:89222514 (GRCh38)
Structure: AlphaFold pLDDT 89.74

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

Disease context

lysosomal acid lipase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Wolman disease cholesteryl ester storage disease

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.Ser297Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
LIPA p.Ser297fs Pathogenic/Likely pathogenic ★★ same residue
LIPA p.Ser297Cys 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

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-ser297 (accessed [today's date]).

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