Is LIPA p.Phe308Val (c.922T>G) pathogenic?

LIPA p.Phe308Val (c.922T>G) is classified Conflicting classifications of pathogenicity in LIPA (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-08-01). AlphaMissense: likely pathogenic (0.8527); Absent from gnomAD v4.1; Associated with Wolman disease.

What condition is associated with LIPA p.Phe308Val (c.922T>G)?

LIPA p.Phe308Val (c.922T>G) is associated with Wolman disease, lysosomal acid lipase deficiency (ClinVar).

How common is LIPA p.Phe308Val (c.922T>G) in the general population?

LIPA p.Phe308Val (c.922T>G) is absent from gnomAD v4.1 (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.Phe308Val (c.922T>G)?

AlphaMissense predicts likely pathogenic (score 0.8527) — an in-silico prediction, not a clinical call.

LIPA p.Phe308Val

c.922T>G · rs751625944 · VCV695044

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8527 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Wolman disease

Computational evidence

Protein change
AlphaMissense	0.8527	likely pathogenic · top 1% in LIPA
REVEL	0.703	pathogenic-leaning
SaProt	LLR -9.94	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Overall
CADD	27.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LIPA
Protein: p.Phe308Val
Coding: c.922T>G
MANE Select: NM_000235
dbSNP: rs751625944
Type: single nucleotide variant
Location: chr10:89215982 (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-phe308val (accessed [today's date]).

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