Is ABCG5 p.Asn437= (c.1311C>T) pathogenic?

ABCG5 p.Asn437= (c.1311C>T) is classified Conflicting classifications of pathogenicity in ABCG5 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-07-18). Ultra-rare (popmax 0.0769%, sas); Associated with Cardiovascular phenotype.

What condition is associated with ABCG5 p.Asn437= (c.1311C>T)?

ABCG5 p.Asn437= (c.1311C>T) is associated with Cardiovascular phenotype, sitosterolemia (ClinVar).

How common is ABCG5 p.Asn437= (c.1311C>T) in the general population?

ABCG5 p.Asn437= (c.1311C>T) is ultra-rare (popmax 0.0769%, sas) (gnomAD).

ABCG5 p.Asn437=

c.1311C>T · rs575266356 · VCV594228

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0769%, sas)

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 -5.5	GERP -3.9
Overall
CADD	3.102	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0769% South Asian · 70/91,074 alleles

Filtering AF 0.0624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0571%

Overall 0.00799% 129/1,614,142 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0769%	1,301
East Asian	0.0245%	4,080
Remaining individualsnot grpmax-eligible	0.008%	12,501
European (non-Finnish)	0.00347%	28,781
Admixed American	0.00167%	60,020
African / African-American	0.00133%	75,040

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.Asn437=
Coding: c.1311C>T
MANE Select: NM_016008 · reported on NM_022436
dbSNP: rs575266356
Type: single nucleotide variant
Location: chr2:43823926 (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-asn437 (accessed [today's date]).

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