Is ABCG5 p.Pro443= (c.1329C>T) pathogenic?

ABCG5 p.Pro443= (c.1329C>T) is classified Likely benign in ABCG5 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0165%, mid); Associated with Cardiovascular phenotype.

What condition is associated with ABCG5 p.Pro443= (c.1329C>T)?

ABCG5 p.Pro443= (c.1329C>T) is associated with Cardiovascular phenotype, sitosterolemia (ClinVar).

How common is ABCG5 p.Pro443= (c.1329C>T) in the general population?

ABCG5 p.Pro443= (c.1329C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

ABCG5 p.Pro443=

c.1329C>T · rs201620171 · VCV1770078

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 -0.61	GERP -3.9
Overall
CADD	5.096	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,058 alleles

Filtering AF 0.00994% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00931%

Overall 0.00954% 154/1,613,774 alleles · ultra-rare exomes 145/1,461,564 · genomes 9/152,210 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,058
European (non-Finnish)	0.0115%	8,676
African / African-American	0.00666%	15,005
Remaining individualsnot grpmax-eligible	0.0064%	15,621
East Asian	0.00446%	22,406
South Asian	0.0044%	22,751
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,598
Admixed American	0.00167%	59,980

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.Pro443=
Coding: c.1329C>T
MANE Select: NM_022436
dbSNP: rs201620171
Type: single nucleotide variant
Location: chr2:43822931 (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 443: the abc transmembrane type-2 domain; an α-helix

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.Pro443Ser Uncertain significance ★★ 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
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-pro443 (accessed [today's date]).

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