Is ABCG5 p.Glu77Ter (c.229G>T) pathogenic?

ABCG5 p.Glu77Ter (c.229G>T) is classified Pathogenic in ABCG5 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-11-26). Very rare (popmax 0.00439%, sas); Associated with ABCG5-related disorder.

What condition is associated with ABCG5 p.Glu77Ter (c.229G>T)?

ABCG5 p.Glu77Ter (c.229G>T) is associated with ABCG5-related disorder, sitosterolemia 2 (ClinVar).

How common is ABCG5 p.Glu77Ter (c.229G>T) in the general population?

ABCG5 p.Glu77Ter (c.229G>T) is very rare (popmax 0.00439%, sas) (gnomAD).

ABCG5 p.Glu77Ter

c.229G>T · rs119480070 · VCV4981

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Conditions

ABCG5-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 13
Splicing
SpliceAI	Δ0.27	donor loss, 36 bp away · masked 0 · deltas
Pangolin	Δ0.42	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.9	GERP 1.6, phastCons 1
Overall
CADD	38.0	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 0.00439% South Asian · 4/91,088 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000248% 4/1,614,028 alleles · very rare

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.Glu77Ter
Coding: c.229G>T
MANE Select: NM_022436
dbSNP: rs119480070
Type: single nucleotide variant
Location: chr2:43837870 (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 77: the abc transporter domain; a β-strand

Full ABCG5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ABCG5-related disorder

Also linked: sitosterolemia 2

Similar variants

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.Arg243Ter Pathogenic ★★ same condition
ABCG5 p.Arg389His Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABCG5 p.Arg408Ter Pathogenic/Likely pathogenic ★★ same condition
ABCG5 p.Arg419His Pathogenic ★★ ⚠ same condition
ABCG5 p.Arg446Ter 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-glu77ter (accessed [today's date]).

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