Is ABCG8 p.Gln183fs (c.547del) pathogenic?

ABCG8 p.Gln183fs (c.547del) is classified Pathogenic/Likely pathogenic in ABCG8 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-02). Ultra-rare (popmax 0.0367%, amr); Associated with sitosterolemia 1.

What condition is associated with ABCG8 p.Gln183fs (c.547del)?

ABCG8 p.Gln183fs (c.547del) is associated with sitosterolemia 1 (ClinVar).

How common is ABCG8 p.Gln183fs (c.547del) in the general population?

ABCG8 p.Gln183fs (c.547del) is ultra-rare (popmax 0.0367%, amr) (gnomAD).

How is Sitosterolemia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ABCG8 p.Gln183fs

c.547del · rs387906323 · VCV4971

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0367%, amr)

Conditions

sitosterolemia 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 1.4, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0367% Admixed American · 22/60,012 alleles

Filtering AF 0.0248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0209%

Overall 0.00136% 22/1,614,056 alleles · ultra-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: ABCG8
Protein: p.Gln183fs
Coding: c.547del
MANE Select: NM_022437
dbSNP: rs387906323
Type: Deletion
Location: chr2:43851806 (GRCh38)
Gene constraint: LOEUF 1.329 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.94 · 8 PDB
Residue 183: the abc transporter domain; an α-helix

Full ABCG8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

sitosterolemia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Sitosterolemia (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

ABCG8 p.Gln137fs Pathogenic/Likely pathogenic ★★ same condition
ABCG8 p.Leu482fs Pathogenic ★★ same condition
ABCG8 c.1411+90del Benign ★★ same condition
ABCG8 p.Asp636fs Likely pathogenic ★ same condition
ABCG8 p.Ser214fs Likely pathogenic ★ same condition
ABCG8 c.64-2A>G Pathogenic ★★ same condition
ABCG8 c.965-1G>C Pathogenic ★★ same condition
ABCG8 p.Arg164Ter 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/abcg8-p-gln183fs (accessed [today's date]).

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