Is LIPA p.Phe228= (c.684T>C) pathogenic?

LIPA p.Phe228= (c.684T>C) is classified Likely benign in LIPA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-03-15). Absent from gnomAD v4.1; Associated with LIPA-related disorder.

What condition is associated with LIPA p.Phe228= (c.684T>C)?

LIPA p.Phe228= (c.684T>C) is associated with LIPA-related disorder (ClinVar).

How common is LIPA p.Phe228= (c.684T>C) in the general population?

LIPA p.Phe228= (c.684T>C) is absent from gnomAD v4.1 (gnomAD).

LIPA p.Phe228=

c.684T>C · rs2495580164 · VCV3047928

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

LIPA-related disorder

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 1.2	GERP -0.63, phastCons 0.99
Overall
CADD	7.921	PHRED · no single calibrated threshold — expert panels disagree

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.Phe228=
Coding: c.684T>C
MANE Select: NM_000235
dbSNP: rs2495580164
Type: single nucleotide variant
Location: chr10:89223822 (GRCh38)
Structure: AlphaFold pLDDT 89.74

Full LIPA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

LIPA-related disorder

Similar variants

LIPA p.Phe228Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
LIPA p.Gln298= Pathogenic/Likely pathogenic ★★ same condition
LIPA p.Phe228fs Pathogenic ★★ same residue
LIPA p.Trp125Ter Likely pathogenic ★ same condition
LIPA p.His173= Likely benign same condition
LIPA p.Asn161fs Pathogenic ★★ same condition
LIPA p.Thr177fs Likely pathogenic same condition
LIPA c.111+1G>A Pathogenic/Likely pathogenic ★★ same type

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-phe228 (accessed [today's date]).

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