Is LIPA p.Ser341= (c.1023C>T) pathogenic?

LIPA p.Ser341= (c.1023C>T) is classified Likely benign in LIPA (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-04-21). Ultra-rare (popmax 0.0187%, afr); Associated with Wolman disease.

What condition is associated with LIPA p.Ser341= (c.1023C>T)?

LIPA p.Ser341= (c.1023C>T) is associated with Wolman disease, lysosomal acid lipase deficiency (ClinVar).

How common is LIPA p.Ser341= (c.1023C>T) in the general population?

LIPA p.Ser341= (c.1023C>T) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

How is Lysosomal acid lipase deficiency inherited?

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

LIPA p.Ser341=

c.1023C>T · rs747984396 · VCV748207

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Conditions

Wolman disease

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 -2.6	GERP -3.9
Overall
CADD	0.527	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% African / African-American · 14/74,910 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00905%

Overall 0.00229% 37/1,613,968 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,351
Remaining individualsnot grpmax-eligible	0.0048%	20,828
South Asian	0.0022%	45,540
European (non-Finnish)	0.00153%	65,554

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.Ser341=
Coding: c.1023C>T
MANE Select: NM_006552 · reported on NM_000235
dbSNP: rs747984396
Type: single nucleotide variant
Location: chr10:89215005 (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

Also linked: lysosomal acid lipase deficiency

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 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
LIPA c.894+1G>A Pathogenic ★★ same condition
LIPA p.Ala307Asp 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-ser341 (accessed [today's date]).

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