Is ABCG5 p.Thr151= (c.453C>A) pathogenic?

ABCG5 p.Thr151= (c.453C>A) is classified Likely benign in ABCG5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-31). Ultra-rare (popmax 0.0197%, amr); Associated with sitosterolemia.

What condition is associated with ABCG5 p.Thr151= (c.453C>A)?

ABCG5 p.Thr151= (c.453C>A) is associated with sitosterolemia (ClinVar).

How common is ABCG5 p.Thr151= (c.453C>A) in the general population?

ABCG5 p.Thr151= (c.453C>A) is ultra-rare (popmax 0.0197%, amr) (gnomAD).

How is Sitosterolemia inherited?

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

ABCG5 p.Thr151=

c.453C>A · rs753629544 · VCV1741321

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0197%, amr)

Conditions

sitosterolemia

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 -11	GERP -3.5
Overall
CADD	3.318	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0197% Admixed American · 11/55,886 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00848%

Overall 0.00233% 37/1,590,336 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0311%	3,218
Admixed Americangrpmax	0.0197%	5,081
Remaining individualsnot grpmax-eligible	0.00487%	20,552
European (non-Finnish)	0.0012%	83,616

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr151=
Coding: c.453C>A
MANE Select: NM_022436
dbSNP: rs753629544
Type: single nucleotide variant
Location: chr2:43831817 (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 151: the abc transporter domain; an α-helix

Full ABCG5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Sitosterolemia (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

ABCG5 p.Thr151Ser Uncertain significance ★★ ⚠ same residue
ABCG5 p.Thr151Pro Uncertain significance ★ ⚠ same residue
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
ABCG5 p.Arg183Ter Pathogenic/Likely pathogenic ★★ same condition
ABCG5 p.Arg243Ter Pathogenic ★★ same condition
ABCG5 p.Arg389His Pathogenic/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/abcg5-p-thr151 (accessed [today's date]).

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