Is ABCG5 p.Arg50Cys (c.148C>T) pathogenic?

ABCG5 p.Arg50Cys (c.148C>T) is classified Benign/Likely benign in ABCG5 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-03-05). AlphaMissense: likely benign (0.1025); Common (popmax 9.17%, amr) — too common for a highly-penetrant pathogenic allele; Associated with sitosterolemia.

What condition is associated with ABCG5 p.Arg50Cys (c.148C>T)?

ABCG5 p.Arg50Cys (c.148C>T) is associated with sitosterolemia, sitosterolemia 1 (ClinVar).

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.Arg50Cys (c.148C>T)?

AlphaMissense predicts likely benign (score 0.1025) — an in-silico prediction, not a clinical call.

ABCG5 p.Arg50Cys

Q: How common is ABCG5 p.Arg50Cys (c.148C>T) in the general population?

ABCG5 p.Arg50Cys (c.148C>T) is common (popmax 9.17%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.148C>T · rs6756629 · VCV286793

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

AlphaMissense

likely benign

0.1025 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 9.17%, amr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

sitosterolemia

Computational evidence

Protein change
AlphaMissense	0.1025	likely benign
REVEL	0.332	indeterminate
SaProt	LLR -8.01	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 0.67, phastCons 0.92
Regional constraint	o/e 1.09	unconstrained · MANE · 26 kb · p 0.0064 · regional, not allelic
Overall
CADD	24.3	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 9.17% Admixed American · 5,500/60,006 alleles

Filtering AF 8.96% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.88%

Overall 6.3% 101,698/1,613,816 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	9.17%	11
Ashkenazi Jewishnot grpmax-eligible	8.77%	11
Finnishnot grpmax-eligible	8.67%	12
African / African-American	8.08%	12
Remaining individualsnot grpmax-eligible	6.49%	15
European (non-Finnish)	6.27%	16
Middle Eastern	6.02%	17
Amishnot grpmax-eligible	4.07%	25
South Asian	3.35%	30
East Asian	1.02%	98

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.Arg50Cys
Coding: c.148C>T
MANE Select: NM_022436
dbSNP: rs6756629
Type: single nucleotide variant
Location: chr2:43837951 (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 50: a UniProt-annotated variant site (in)

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 1

For Sitosterolemia (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

ABCG5 p.Arg50= Likely benign ★★ same residue
ABCG5 p.Arg50His Uncertain significance ★ ⚠ same residue
ABCG5 p.Arg50Leu Uncertain significance ★ ⚠ same residue
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-arg50cys (accessed [today's date]).

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