Is ABCG5 p.Ala98Cys (c.292_293delinsTG) pathogenic?

ABCG5 p.Ala98Cys (c.292293delinsTG) is classified Uncertain significance in ABCG5 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-11-24). Absent from gnomAD; Associated with sitosterolemia 1.

What condition is associated with ABCG5 p.Ala98Cys (c.292_293delinsTG)?

ABCG5 p.Ala98Cys (c.292_293delinsTG) is associated with sitosterolemia 1, sitosterolemia, sitosterolemia 2 (ClinVar).

How common is ABCG5 p.Ala98Cys (c.292_293delinsTG) in the general population?

ABCG5 p.Ala98Cys (c.292_293delinsTG) is absent from gnomAD (gnomAD).

How is Sitosterolemia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ABCG5 p.Ala98Cys

c.292_293delinsTG · rs1667984117 · VCV1028260

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

sitosterolemia 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.8	GERP 1.6, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 26 kb · p 0.0064 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ABCG5
Protein: p.Ala98Cys
Coding: c.292_293delinsTG
MANE Select: NM_022436
dbSNP: rs1667984117
Type: Indel
Location: chr2:43832056 (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 98: the abc transporter domain; an α-helix

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

Disease context

sitosterolemia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: sitosterolemia sitosterolemia 2

For Sitosterolemia (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

ABCG5 p.Ala98Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCG5 p.Ala98Ser Uncertain significance ★ ⚠ 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
ABCG5 p.Arg243Ter 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-ala98cys (accessed [today's date]).

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