Is ABCG5 p.Asn285Ser (c.854A>G) pathogenic?

ABCG5 p.Asn285Ser (c.854A>G) is classified Uncertain significance in ABCG5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-09). AlphaMissense: likely benign (0.0486); Ultra-rare (popmax 0.0657%, mid); Associated with sitosterolemia.

What condition is associated with ABCG5 p.Asn285Ser (c.854A>G)?

ABCG5 p.Asn285Ser (c.854A>G) is associated with sitosterolemia, sitosterolemia 2 (ClinVar).

How common is ABCG5 p.Asn285Ser (c.854A>G) in the general population?

ABCG5 p.Asn285Ser (c.854A>G) is ultra-rare (popmax 0.0657%, mid) (gnomAD).

How is Sitosterolemia inherited?

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

What do computational predictors say about ABCG5 p.Asn285Ser (c.854A>G)?

AlphaMissense predicts likely benign (score 0.0486) — an in-silico prediction, not a clinical call.

ABCG5 p.Asn285Ser

c.854A>G · rs975612815 · VCV2690816

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0486 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0657%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

sitosterolemia

Computational evidence

Protein change
AlphaMissense	0.0486	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -5.04	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 -4.9	GERP -3.6
Regional constraint	o/e 1.09	unconstrained · MANE · 26 kb · p 0.0064 · regional, not allelic
Overall
CADD	0.037	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 0.0657% Middle Eastern · 4/6,084 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00186% 30/1,613,972 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0657%	1,521
African / African-American	0.0133%	7,494
South Asian	0.00878%	11,384
Remaining individualsnot grpmax-eligible	0.0032%	31,242
European (non-Finnish)	0.000508%	196,665

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.Asn285Ser
Coding: c.854A>G
MANE Select: NM_022436
dbSNP: rs975612815
Type: single nucleotide variant
Location: chr2:43824939 (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 285: the abc transporter domain; an α-helix

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

Disease context

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

Also linked: sitosterolemia 2

For Sitosterolemia (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

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ABCG5 p.Arg183Ter Pathogenic/Likely pathogenic ★★ same condition
ABCG5 p.Arg243Ter Pathogenic ★★ same condition
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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-asn285ser (accessed [today's date]).

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