Is ABCA1 p.Gln732= (c.2196G>A) pathogenic?

ABCA1 p.Gln732= (c.2196G>A) is classified Conflicting classifications of pathogenicity in ABCA1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-04). Rare (popmax 0.325%, eas); Associated with hypoalphalipoproteinemia, primary, 1.

What condition is associated with ABCA1 p.Gln732= (c.2196G>A)?

ABCA1 p.Gln732= (c.2196G>A) is associated with hypoalphalipoproteinemia, primary, 1, Tangier disease (ClinVar).

How common is ABCA1 p.Gln732= (c.2196G>A) in the general population?

ABCA1 p.Gln732= (c.2196G>A) is rare (popmax 0.325%, eas) (gnomAD).

How is Apolipoprotein A-I deficiency inherited?

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

ABCA1 p.Gln732=

c.2196G>A · rs187695583 · VCV364435

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.325%, eas)

Conditions

hypoalphalipoproteinemia, primary, 1

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 1.1	GERP 1.2, phastCons 1
Overall
CADD	11.75	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.325% East Asian · 146/44,886 alleles

Filtering AF 0.282% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.266%

Overall 0.00929% 150/1,614,200 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.325%	307
European (non-Finnish)	0.000339%	295,009

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: ABCA1
Protein: p.Gln732=
Coding: c.2196G>A
MANE Select: NM_005502
dbSNP: rs187695583
Type: single nucleotide variant
Location: chr9:104827089 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB
Residue 732: an α-helix

Full ABCA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypoalphalipoproteinemia, primary, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Tangier disease

For Apolipoprotein A-I deficiency (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages

Similar variants

ABCA1 c.5237+3A>C Likely pathogenic ★★ same condition
ABCA1 p.Arg2080Trp Likely pathogenic ★★ same condition
ABCA1 p.Arg587Trp Pathogenic/Likely pathogenic ★★ same condition
ABCA1 p.Asn1800His Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABCA1 c.*2330A>T Uncertain significance ★★ same condition
ABCA1 c.*379C>T Uncertain significance ★★ same condition
ABCA1 p.Arg126Cys Uncertain significance ★★ ⚠ same condition
ABCA1 p.Arg1342Trp Uncertain significance ★★ ⚠ 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/abca1-p-gln732 (accessed [today's date]).

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