Is ABCA1 p.Arg587Trp (c.1759C>T) pathogenic?

ABCA1 p.Arg587Trp (c.1759C>T) is classified Pathogenic/Likely pathogenic in ABCA1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-08). AlphaMissense: likely pathogenic (0.8518); Very rare (popmax 0.00896%, eas); Associated with Autosomal dominant and autosomal recessive ABCA1-related disorders.

How common is ABCA1 p.Arg587Trp (c.1759C>T) in the general population?

ABCA1 p.Arg587Trp (c.1759C>T) is very rare (popmax 0.00896%, eas) (gnomAD).

What do computational predictors say about ABCA1 p.Arg587Trp (c.1759C>T)?

AlphaMissense predicts likely pathogenic (score 0.8518) — an in-silico prediction, not a clinical call.

ABCA1 p.Arg587Trp

Q: What condition is associated with ABCA1 p.Arg587Trp (c.1759C>T)?

ABCA1 p.Arg587Trp (c.1759C>T) is associated with Autosomal dominant and autosomal recessive ABCA1-related disorders, Tangier disease (ClinVar).

c.1759C>T · rs2853574 · VCV632033

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.8518 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00896%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Autosomal dominant and autosomal recessive ABCA1-related disorders

Computational evidence

Protein change
AlphaMissense	0.8518	likely pathogenic ✓ concordant with ClinVar
REVEL	0.954	strongly pathogenic-leaning
SaProt	LLR -11.31	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.6	GERP 1.2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 81 kb · p 0.081 · regional, not allelic
Overall
CADD	29.6	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 0.00896% East Asian · 4/44,664 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00233%

Overall 0.0031% 50/1,610,888 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00896%	11,166
Finnishnot grpmax-eligible	0.00474%	21,103
European (non-Finnish)	0.00348%	28,772
Remaining individualsnot grpmax-eligible	0.0016%	62,412
African / African-American	0.00136%	73,758

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.Arg587Trp
Coding: c.1759C>T
MANE Select: NM_005502
dbSNP: rs2853574
Type: single nucleotide variant
Location: chr9:104831058 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB
Residue 587: an α-helix; the 'gateway domain' region; a UniProt-annotated variant site (in tgd)

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

Disease context

Autosomal dominant and autosomal recessive ABCA1-related disorders

Also linked: Tangier disease

Similar variants

ABCA1 p.Arg2080Trp 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
ABCA1 p.Arg999Cys Uncertain significance ★★ ⚠ same condition
ABCA1 p.Cys23Tyr 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-arg587trp (accessed [today's date]).

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