Is LIPA p.Val206= (c.618C>G) pathogenic?

LIPA p.Val206= (c.618C>G) is classified Likely benign in LIPA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-17). Very rare (popmax 0.00223%, eas); Associated with Cardiovascular phenotype.

What condition is associated with LIPA p.Val206= (c.618C>G)?

LIPA p.Val206= (c.618C>G) is associated with Cardiovascular phenotype, Wolman disease (ClinVar).

How common is LIPA p.Val206= (c.618C>G) in the general population?

LIPA p.Val206= (c.618C>G) is very rare (popmax 0.00223%, eas) (gnomAD).

LIPA p.Val206=

c.618C>G · rs763651849 · VCV1553890

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, 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 -2.4	GERP -3.9
Overall
CADD	0.084	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,886 alleles

Overall 6.2e-05% 1/1,614,162 alleles · very rare exomes 1/1,461,858 · genomes 0/152,304 · joint denominator

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.Val206=
Coding: c.618C>G
MANE Select: NM_000235
dbSNP: rs763651849
Type: single nucleotide variant
Location: chr10:89225149 (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.Val206Ile Uncertain significance ★★ ⚠ same residue
LIPA p.Val206Phe Uncertain significance ★ ⚠ same residue
LIPA p.Val206Leu Likely benign ★ same residue
LIPA p.Val206dup Likely pathogenic ★★ same residue
LIPA p.Val206fs 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

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-val206 (accessed [today's date]).

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