Is ABCA1 p.Arg230Cys (c.688C>T) pathogenic?

ABCA1 p.Arg230Cys (c.688C>T) is classified Benign in ABCA1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1703); Common (popmax 7.31%, amr) — too common for a highly-penetrant pathogenic allele; Associated with Tangier disease.

What condition is associated with ABCA1 p.Arg230Cys (c.688C>T)?

ABCA1 p.Arg230Cys (c.688C>T) 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.

What do computational predictors say about ABCA1 p.Arg230Cys (c.688C>T)?

AlphaMissense predicts likely benign (score 0.1703) — an in-silico prediction, not a clinical call.

ABCA1 p.Arg230Cys

Q: How common is ABCA1 p.Arg230Cys (c.688C>T) in the general population?

ABCA1 p.Arg230Cys (c.688C>T) is common (popmax 7.31%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.688C>T · rs9282541 · VCV364456

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.1703 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 7.31%, amr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Tangier disease

Computational evidence

Protein change
AlphaMissense	0.1703	likely benign
REVEL	0.465	indeterminate
SaProt	LLR -5.88	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.3	GERP 2.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 81 kb · p 0.081 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.31% Admixed American · 4,385/60,016 alleles

Filtering AF 7.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.05%

Overall 0.286% 4,623/1,614,124 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	7.31%	14
Remaining individualsnot grpmax-eligible	0.181%	553
African / African-American	0.0813%	1,230
European (non-Finnish)	0.005%	20,000
East Asian	0.00446%	22,445
South Asian	0.00329%	30,359

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.Arg230Cys
Coding: c.688C>T
MANE Select: NM_005502
dbSNP: rs9282541
Type: single nucleotide variant
Location: chr9:104858554 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB
Residue 230: an α-helix; a disulfide bond; a UniProt-annotated variant site (in)

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.Arg230His Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCA1 p.Arg230Pro Uncertain significance ★ same residue
ABCA1 p.Arg230Ser Uncertain significance ★ ⚠ 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-arg230cys (accessed [today's date]).

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