Is LIPA p.Thr55fs (c.164_165del) pathogenic?

LIPA p.Thr55fs (c.164165del) is classified Likely pathogenic in LIPA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-28). Very rare (popmax 0.0011%, sas); Associated with lysosomal acid lipase deficiency.

What condition is associated with LIPA p.Thr55fs (c.164_165del)?

LIPA p.Thr55fs (c.164_165del) is associated with lysosomal acid lipase deficiency (ClinVar).

How common is LIPA p.Thr55fs (c.164_165del) in the general population?

LIPA p.Thr55fs (c.164_165del) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Lysosomal acid lipase deficiency inherited?

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

LIPA p.Thr55fs

c.164_165del · VCV4069973

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

lysosomal acid lipase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.68	GERP -1.6

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,884 alleles

Overall 6.88e-05% 1/1,453,908 alleles · very rare

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.Thr55fs
Coding: c.164_165del
MANE Select: NM_006552 · reported on NM_000235
Type: Deletion
Location: chr10:89245740 (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

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.Asn161fs Pathogenic ★★ same condition
LIPA p.Leu132_Ser133insTer Pathogenic ★★ same condition
LIPA p.Leu394fs Pathogenic/Likely pathogenic ★★ same condition
LIPA p.Phe228fs Pathogenic ★★ same condition
LIPA p.Thr327fs Pathogenic/Likely pathogenic ★★ same condition
LIPA p.Gly105fs Likely pathogenic ★ same condition
LIPA p.Leu160fs Likely pathogenic ★ same condition
LIPA p.Leu294fs 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-thr55fs (accessed [today's date]).

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