Is ABCG5 p.Ile523= (c.1569C>A) pathogenic?

ABCG5 p.Ile523= (c.1569C>A) is classified Likely benign in ABCG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-20). Very rare (popmax 0.00329%, sas); Associated with Cardiovascular phenotype.

What condition is associated with ABCG5 p.Ile523= (c.1569C>A)?

ABCG5 p.Ile523= (c.1569C>A) is associated with Cardiovascular phenotype (ClinVar).

How common is ABCG5 p.Ile523= (c.1569C>A) in the general population?

ABCG5 p.Ile523= (c.1569C>A) is very rare (popmax 0.00329%, sas) (gnomAD).

ABCG5 p.Ile523=

c.1569C>A · rs376969021 · VCV1775431

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

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 -1.1	GERP -3.5
Overall
CADD	0.385	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,070 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000274% 4/1,461,884 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,357
European (non-Finnish)	8.47e-05%	1,180,022

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.Ile523=
Coding: c.1569C>A
MANE Select: NM_022436
dbSNP: rs376969021
Type: single nucleotide variant
Location: chr2:43819995 (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 523: the abc transmembrane type-2 domain; a UniProt-annotated variant site (in); 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

Similar variants

ABCG5 p.Ile523Met Likely benign ★ same residue
ABCG5 p.Ile523Val Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCG5 c.1325-1G>T Likely pathogenic ★★ same condition
ABCG5 p.Gln251Ter Pathogenic ★★ same condition
ABCG5 p.Glu146Ter Pathogenic ★★ same condition
ABCG5 p.Ala170Asp Uncertain significance ★★ ⚠ same condition
ABCG5 p.Ala264Val Uncertain significance ★★ ⚠ same condition
ABCG5 p.Ala278Glu Uncertain significance ★★ ⚠ 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-ile523 (accessed [today's date]).

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