Is ABCG5 p.Arg243Gln (c.728G>A) pathogenic?

ABCG5 p.Arg243Gln (c.728G>A) is classified Uncertain significance in ABCG5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-29). AlphaMissense: likely benign (0.1527); Very rare (popmax 0.00769%, sas); Associated with Cardiovascular phenotype.

What condition is associated with ABCG5 p.Arg243Gln (c.728G>A)?

ABCG5 p.Arg243Gln (c.728G>A) is associated with Cardiovascular phenotype, sitosterolemia 2 (ClinVar).

How common is ABCG5 p.Arg243Gln (c.728G>A) in the general population?

ABCG5 p.Arg243Gln (c.728G>A) is very rare (popmax 0.00769%, sas) (gnomAD).

What do computational predictors say about ABCG5 p.Arg243Gln (c.728G>A)?

AlphaMissense predicts likely benign (score 0.1527) — an in-silico prediction, not a clinical call.

ABCG5 p.Arg243Gln

c.728G>A · rs774178234 · VCV1693811

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1527 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1527	likely benign
REVEL	0.267	benign-leaning
SaProt	LLR -9.36	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 26 kb · p 0.0064 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00769% South Asian · 7/91,082 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00112% 18/1,613,948 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,012
East Asian	0.00223%	44,880
Remaining individualsnot grpmax-eligible	0.0016%	62,482
Finnishnot grpmax-eligible	0.00156%	64,000
European (non-Finnish)	0.000678%	147,505

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.Arg243Gln
Coding: c.728G>A
MANE Select: NM_022436
dbSNP: rs774178234
Type: single nucleotide variant
Location: chr2:43826428 (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 243: the abc transporter domain

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 2

Similar variants

ABCG5 p.Arg243Ter Pathogenic ★★ same residue
ABCG5 p.Arg243Leu Uncertain significance ★★ ⚠ same residue
ABCG5 p.Arg243= Likely benign ★ same residue
ABCG5 c.1325-1G>T Likely pathogenic ★★ same condition
ABCG5 c.1464-1G>C Pathogenic/Likely pathogenic ★★ same condition
ABCG5 c.1762+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCG5 p.Arg183Ter Pathogenic/Likely 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-arg243gln (accessed [today's date]).

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