Is ABCG5 p.Arg61Gln (c.182G>A) pathogenic?

ABCG5 p.Arg61Gln (c.182G>A) is classified Conflicting classifications of pathogenicity in ABCG5 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2024-12-21). AlphaMissense: likely benign (0.0698); Ultra-rare (popmax 0.0164%, mid); Associated with sitosterolemia 1.

What condition is associated with ABCG5 p.Arg61Gln (c.182G>A)?

ABCG5 p.Arg61Gln (c.182G>A) is associated with sitosterolemia 1, sitosterolemia, sitosterolemia 2 (ClinVar).

How common is ABCG5 p.Arg61Gln (c.182G>A) in the general population?

ABCG5 p.Arg61Gln (c.182G>A) is ultra-rare (popmax 0.0164%, 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.Arg61Gln (c.182G>A)?

AlphaMissense predicts likely benign (score 0.0698) — an in-silico prediction, not a clinical call.

ABCG5 p.Arg61Gln

c.182G>A · rs149599171 · VCV336055

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0698 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

sitosterolemia 1

Computational evidence

Protein change
AlphaMissense	0.0698	likely benign
REVEL	0.185	benign-leaning
SaProt	LLR -7.49	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.69	GERP -0.3
Regional constraint	o/e 1.09	unconstrained · MANE · 26 kb · p 0.0064 · regional, not allelic
Overall
CADD	10.99	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00749% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.007%

Overall 0.00874% 141/1,613,994 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0709%	1,410
Middle Easterngrpmax	0.0164%	6,082
Remaining individualsnot grpmax-eligible	0.0096%	10,414
European (non-Finnish)	0.0089%	11,238
Admixed American	0.00667%	15,002
African / African-American	0.00534%	18,730

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg61Gln
Coding: c.182G>A
MANE Select: NM_022436
dbSNP: rs149599171
Type: single nucleotide variant
Location: chr2:43837917 (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 61: the abc transporter domain

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.Arg61Trp Uncertain significance ★★ ⚠ same residue
ABCG5 p.Arg61= 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
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-arg61gln (accessed [today's date]).

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