Is ABCG5 p.Leu15= (c.45C>G) pathogenic?

ABCG5 p.Leu15= (c.45C>G) is classified Likely benign in ABCG5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-31). Very rare (popmax 0.000424%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with ABCG5 p.Leu15= (c.45C>G)?

ABCG5 p.Leu15= (c.45C>G) is associated with Cardiovascular phenotype, sitosterolemia (ClinVar).

How common is ABCG5 p.Leu15= (c.45C>G) in the general population?

ABCG5 p.Leu15= (c.45C>G) is very rare (popmax 0.000424%, nfe) (gnomAD).

ABCG5 p.Leu15=

c.45C>G · rs932531973 · VCV1589242

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

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 0.14	GERP 0.67, phastCons 0.001
Overall
CADD	0.987	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,934 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,264 alleles · very rare

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: ABCG5
Protein: p.Leu15=
Coding: c.45C>G
MANE Select: NM_022436
dbSNP: rs932531973
Type: single nucleotide variant
Location: chr2:43838635 (GRCh38)
Gene constraint: LOEUF 1.219 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.48 · 8 PDB
Residue 15: the 'disordered' region

Full ABCG5 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: sitosterolemia

Similar variants

ABCG5 p.Leu15Val Uncertain significance ★★ ⚠ same residue
ABCG5 p.Leu15Ile Uncertain significance ★ ⚠ same residue
ABCG5 p.Leu15Phe Uncertain significance ★ ⚠ same residue
ABCG8 p.Ala15Thr Likely benign ★ same residue
ABCG5 c.1325-1G>T Likely pathogenic ★★ same condition
ABCG5 c.1762+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCG5 c.634+1G>C Likely pathogenic ★★ same condition
ABCG5 c.904+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/abcg5-p-leu15 (accessed [today's date]).

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