Is LIPA p.Gly343Asp (c.1028G>A) pathogenic?

LIPA p.Gly343Asp (c.1028G>A) is classified Uncertain significance in LIPA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-08). AlphaMissense: likely benign (0.3373); Ultra-rare (popmax 0.02%, amr); Associated with Wolman disease.

What condition is associated with LIPA p.Gly343Asp (c.1028G>A)?

LIPA p.Gly343Asp (c.1028G>A) is associated with Wolman disease (ClinVar).

How common is LIPA p.Gly343Asp (c.1028G>A) in the general population?

LIPA p.Gly343Asp (c.1028G>A) is ultra-rare (popmax 0.02%, amr) (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.Gly343Asp (c.1028G>A)?

AlphaMissense predicts likely benign (score 0.3373) — an in-silico prediction, not a clinical call.

LIPA p.Gly343Asp

c.1028G>A · rs780007692 · VCV2077014

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3373 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Wolman disease

Computational evidence

Protein change
AlphaMissense	0.3373	likely benign
REVEL	0.298	indeterminate
SaProt	LLR -14.43	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.18	GERP -1.9
Overall
CADD	12.56	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 0.02% Admixed American · 12/59,996 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.00105% 17/1,613,986 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.02%	5,000
South Asian	0.0011%	91,088
European (non-Finnish)	0.000339%	294,997

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.Gly343Asp
Coding: c.1028G>A
MANE Select: NM_006552 · reported on NM_000235
dbSNP: rs780007692
Type: single nucleotide variant
Location: chr10:89215000 (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.Gly343dup Likely 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
LIPA c.894+1G>A 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-gly343asp (accessed [today's date]).

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