Is LIPA p.Asp352= (c.1056C>T) pathogenic?

LIPA p.Asp352= (c.1056C>T) is classified Conflicting classifications of pathogenicity in LIPA (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-05-12). Very rare (popmax 0.00445%, eas); Associated with Cardiovascular phenotype.

What condition is associated with LIPA p.Asp352= (c.1056C>T)?

LIPA p.Asp352= (c.1056C>T) is associated with Cardiovascular phenotype, Wolman disease (ClinVar).

How common is LIPA p.Asp352= (c.1056C>T) in the general population?

LIPA p.Asp352= (c.1056C>T) is very rare (popmax 0.00445%, eas) (gnomAD).

LIPA p.Asp352=

c.1056C>T · rs1564748504 · VCV598726

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00445%, eas)

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 0.11	GERP -2, phastCons 0.001
Overall
CADD	5.902	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00445% East Asian · 2/44,900 alleles

Filtering AF 0.000738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.00031% 5/1,613,846 alleles · very rare exomes 4/1,461,724 · genomes 1/152,122 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00445%	22,450
African / African-American	0.00134%	74,894
European (non-Finnish)	0.00017%	589,936

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.Asp352=
Coding: c.1056C>T
MANE Select: NM_000235
dbSNP: rs1564748504
Type: single nucleotide variant
Location: chr10:89214972 (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

Similar variants

LIPA p.Asp352Asn Uncertain significance ★ ⚠ same residue
LIPA p.Asp352del Pathogenic ★★ 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-asp352 (accessed [today's date]).

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