Is ABCA1 p.Arg1228= (c.3684G>A) pathogenic?

ABCA1 p.Arg1228= (c.3684G>A) is classified Benign in ABCA1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). Common (popmax 19.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Tangier disease.

What condition is associated with ABCA1 p.Arg1228= (c.3684G>A)?

ABCA1 p.Arg1228= (c.3684G>A) is associated with Tangier disease, hypoalphalipoproteinemia, primary, 1 (ClinVar).

How is Tangier disease inherited?

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

ABCA1 p.Arg1228=

Q: How common is ABCA1 p.Arg1228= (c.3684G>A) in the general population?

ABCA1 p.Arg1228= (c.3684G>A) is common (popmax 19.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3684G>A · rs2230807 · VCV364412

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 19.5%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Tangier disease

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	GERP -3.6, phastCons 0.001
Overall
CADD	5.856	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 19.5% African / African-American · 14,603/74,932 alleles

Filtering AF 19.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 19.1%

Overall 1.05% 16,889/1,614,000 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	19.5%	5
Middle Eastern	1.55%	64
Remaining individualsnot grpmax-eligible	1.38%	72
Admixed American	1.33%	75
Ashkenazi Jewishnot grpmax-eligible	0.101%	987
South Asian	0.0681%	1,469
European (non-Finnish)	0.0372%	2,688
East Asian	0.00223%	44,870

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.Arg1228=
Coding: c.3684G>A
MANE Select: NM_005502
dbSNP: rs2230807
Type: single nucleotide variant
Location: chr9:104816197 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB

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

Disease context

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

Also linked: hypoalphalipoproteinemia, primary, 1

For Tangier disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal

Similar variants

ABCA1 p.Arg1228Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCA1 p.Arg1228Gly Uncertain significance ★ ⚠ same residue
ABCA1 p.Arg1228Trp Likely benign ★ ⚠ same residue
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

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-arg1228 (accessed [today's date]).

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