Is ABCG5 p.His470= (c.1410C>T) pathogenic?

ABCG5 p.His470= (c.1410C>T) is classified Likely benign in ABCG5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0493%, mid); Associated with Cardiovascular phenotype.

What condition is associated with ABCG5 p.His470= (c.1410C>T)?

ABCG5 p.His470= (c.1410C>T) is associated with Cardiovascular phenotype, sitosterolemia (ClinVar).

How common is ABCG5 p.His470= (c.1410C>T) in the general population?

ABCG5 p.His470= (c.1410C>T) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

ABCG5 p.His470=

c.1410C>T · rs369709495 · VCV529882

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.42 · evaluated, not missing
Constraint at this position
Conservation	phyloP -11	GERP -3.9
Overall
CADD	0.036	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0493% Middle Eastern · 3/6,082 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00785%

Overall 0.00787% 127/1,614,048 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,027
East Asian	0.02%	4,988
Admixed American	0.0183%	5,455
European (non-Finnish)	0.00814%	12,292
African / African-American	0.00534%	18,732
Remaining individualsnot grpmax-eligible	0.0048%	20,829
South Asian	0.0011%	91,080

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.His470=
Coding: c.1410C>T
MANE Select: NM_022436
dbSNP: rs369709495
Type: single nucleotide variant
Location: chr2:43822850 (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 470: the abc transmembrane type-2 domain; an α-helix

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

Disease context

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

Also linked: sitosterolemia

Similar variants

ABCG5 p.His470Asp Uncertain significance ★ ⚠ same residue
ABCG5 c.1325-1G>T 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
ABCG5 p.Arg389His Pathogenic/Likely 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-his470 (accessed [today's date]).

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