Is LIPA p.Ser284= (c.852T>G) pathogenic?

LIPA p.Ser284= (c.852T>G) is classified Likely benign in LIPA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-10). Ultra-rare (popmax 0.0165%, mid); Associated with Cardiovascular phenotype.

What condition is associated with LIPA p.Ser284= (c.852T>G)?

LIPA p.Ser284= (c.852T>G) is associated with Cardiovascular phenotype, Wolman disease (ClinVar).

How common is LIPA p.Ser284= (c.852T>G) in the general population?

LIPA p.Ser284= (c.852T>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

LIPA p.Ser284=

c.852T>G · rs778780317 · VCV1585764

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 2.5	GERP 1.9, phastCons 0.87
Overall
CADD	8.518	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,054 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000311% 5/1,609,846 alleles · ultra-rare exomes 5/1,457,494 · genomes 0/152,352 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,054
Remaining individualsnot grpmax-eligible	0.0016%	62,368
European (non-Finnish)	0.000255%	392,019

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.Ser284=
Coding: c.852T>G
MANE Select: NM_000235
dbSNP: rs778780317
Type: single nucleotide variant
Location: chr10:89222553 (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.Ser284Pro Uncertain significance ★ ⚠ same residue
LIPA p.Ser284Phe 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
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-ser284 (accessed [today's date]).

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