Is ABCG5 p.Pro33= (c.99G>A) pathogenic?

ABCG5 p.Pro33= (c.99G>A) is classified Conflicting classifications of pathogenicity in ABCG5 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-18). Rare (popmax 0.101%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ABCG5 p.Pro33= (c.99G>A)?

ABCG5 p.Pro33= (c.99G>A) is associated with Cardiovascular phenotype, sitosterolemia (ClinVar).

How common is ABCG5 p.Pro33= (c.99G>A) in the general population?

ABCG5 p.Pro33= (c.99G>A) is rare (popmax 0.101%, afr) (gnomAD).

ABCG5 p.Pro33=

c.99G>A · rs149907931 · VCV597157

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.101%, afr)

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 -4.4	GERP -3.2
Overall
CADD	6.398	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.101% African / African-American · 76/74,986 alleles

Filtering AF 0.0829% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0762%

Overall 0.0218% 351/1,609,798 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.101%	987
Middle Eastern	0.0498%	2,010
Admixed American	0.0235%	4,259
Remaining individualsnot grpmax-eligible	0.0225%	4,449
European (non-Finnish)	0.0197%	5,081
South Asian	0.0122%	8,200
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,498

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.Pro33=
Coding: c.99G>A
MANE Select: NM_022436
dbSNP: rs149907931
Type: single nucleotide variant
Location: chr2:43838581 (GRCh38)
Gene constraint: LOEUF 1.219 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.48 · 8 PDB

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.Pro33Arg Uncertain significance ★★ ⚠ same residue
ABCG5 p.Pro33Leu Conflicting classifications of pathogenicity ★ ⚠ 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
ABCG5 p.Arg183Ter Pathogenic/Likely pathogenic ★★ same condition
ABCG5 p.Arg243Ter 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-pro33 (accessed [today's date]).

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