Is ABCG5 p.Ser475= (c.1425C>T) pathogenic?

ABCG5 p.Ser475= (c.1425C>T) is classified Likely benign in ABCG5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-14). Ultra-rare (popmax 0.0379%, eas); Associated with Cardiovascular phenotype.

What condition is associated with ABCG5 p.Ser475= (c.1425C>T)?

ABCG5 p.Ser475= (c.1425C>T) is associated with Cardiovascular phenotype, sitosterolemia (ClinVar).

How common is ABCG5 p.Ser475= (c.1425C>T) in the general population?

ABCG5 p.Ser475= (c.1425C>T) is ultra-rare (popmax 0.0379%, eas) (gnomAD).

ABCG5 p.Ser475=

c.1425C>T · rs201506122 · VCV1772351

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0379%, eas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.58	GERP -3.9
Overall
CADD	3.422	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0379% East Asian · 17/44,882 alleles

Filtering AF 0.0241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00415% 67/1,614,156 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0379%	2,640
Ashkenazi Jewishnot grpmax-eligible	0.00675%	14,804
Admixed American	0.005%	20,007
African / African-American	0.004%	25,013
South Asian	0.00329%	30,362
European (non-Finnish)	0.00322%	31,053
Remaining individualsnot grpmax-eligible	0.0016%	62,502

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.Ser475=
Coding: c.1425C>T
MANE Select: NM_016008 · reported on NM_022436
dbSNP: rs201506122
Type: single nucleotide variant
Location: chr2:43822835 (GRCh38)

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

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-ser475 (accessed [today's date]).

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