Is ABCG5 p.Arg243Ter (c.727C>T) pathogenic?

ABCG5 p.Arg243Ter (c.727C>T) is classified Pathogenic in ABCG5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-24). Ultra-rare (popmax 0.0143%, sas); Associated with ABCG5-related disorder.

What condition is associated with ABCG5 p.Arg243Ter (c.727C>T)?

ABCG5 p.Arg243Ter (c.727C>T) is associated with ABCG5-related disorder, sitosterolemia, sitosterolemia 2 (ClinVar).

How common is ABCG5 p.Arg243Ter (c.727C>T) in the general population?

ABCG5 p.Arg243Ter (c.727C>T) is ultra-rare (popmax 0.0143%, sas) (gnomAD).

ABCG5 p.Arg243Ter

c.727C>T · rs119479066 · VCV4977

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, sas)

Conditions

ABCG5-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 13
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1.9, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0143% South Asian · 13/91,082 alleles

Filtering AF 0.00844% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00661%

Overall 0.000929% 15/1,613,926 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0143%	7,006
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	8.47e-05%	1,180,018

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.Arg243Ter
Coding: c.727C>T
MANE Select: NM_022436
dbSNP: rs119479066
Type: single nucleotide variant
Location: chr2:43826429 (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

ABCG5-related disorder

Also linked: sitosterolemia sitosterolemia 2

Similar variants

ABCG5 p.Arg243Gln Uncertain significance ★★ ⚠ same residue
ABCG5 p.Arg243Leu Uncertain significance ★★ ⚠ same residue
ABCG5 p.Arg243= Likely benign ★ same residue
ABCG5 c.1464-1G>C Pathogenic/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

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-arg243ter (accessed [today's date]).

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