Is ABCG8 p.Pro12= (c.36G>A) pathogenic?

ABCG8 p.Pro12= (c.36G>A) is classified Conflicting classifications of pathogenicity in ABCG8 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2019-08-24). Very rare (popmax 0.00296%, nfe); Associated with sitosterolemia 1.

What condition is associated with ABCG8 p.Pro12= (c.36G>A)?

ABCG8 p.Pro12= (c.36G>A) is associated with sitosterolemia 1 (ClinVar).

How common is ABCG8 p.Pro12= (c.36G>A) in the general population?

ABCG8 p.Pro12= (c.36G>A) is very rare (popmax 0.00296%, nfe) (gnomAD).

How is Sitosterolemia inherited?

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

ABCG8 p.Pro12=

c.36G>A · rs368998235 · VCV336061

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00296%, nfe)

Conditions

sitosterolemia 1

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.2	GERP -1.8, phastCons 0.032
Overall
CADD	12.96	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00296% European (non-Finnish) · 34/1,146,826 alleles

Filtering AF 0.00213% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00188%

Overall 0.00239% 37/1,551,170 alleles · very rare exomes 34/1,398,956 · genomes 3/152,214 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00296%	33,730
South Asian	0.00238%	42,024
Remaining individualsnot grpmax-eligible	0.00166%	60,070

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.Pro12=
Coding: c.36G>A
MANE Select: NM_022437
dbSNP: rs368998235
Type: single nucleotide variant
Location: chr2:43839089 (GRCh38)

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

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-pro12 (accessed [today's date]).

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