Is ABCG5 p.His42= (c.126T>C) pathogenic?

ABCG5 p.His42= (c.126T>C) is classified Likely benign in ABCG5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-08-24). Very rare (popmax 0.000255%, nfe); Associated with sitosterolemia.

What condition is associated with ABCG5 p.His42= (c.126T>C)?

ABCG5 p.His42= (c.126T>C) is associated with sitosterolemia (ClinVar).

How common is ABCG5 p.His42= (c.126T>C) in the general population?

ABCG5 p.His42= (c.126T>C) is very rare (popmax 0.000255%, nfe) (gnomAD).

How is Sitosterolemia inherited?

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

ABCG5 p.His42=

c.126T>C · rs1195869739 · VCV1765191

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000255%, nfe)

Conditions

sitosterolemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.6	GERP -3.2
Overall
CADD	0.532	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000255% European (non-Finnish) · 3/1,177,340 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000187% 3/1,606,814 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.His42=
Coding: c.126T>C
MANE Select: NM_022436
dbSNP: rs1195869739
Type: single nucleotide variant
Location: chr2:43838554 (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 42: a β-strand

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

For Sitosterolemia (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

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
ABCG5 p.Arg389His Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABCG5 p.Arg408Ter Pathogenic/Likely pathogenic ★★ same condition
ABCG5 p.Arg419His 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-his42 (accessed [today's date]).

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