Is ABCA1 p.Ala697Thr (c.2089G>A) pathogenic?

ABCA1 p.Ala697Thr (c.2089G>A) is classified Benign/Likely benign in ABCA1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.195); Rare (popmax 0.684%, afr); Associated with Tangier disease.

What condition is associated with ABCA1 p.Ala697Thr (c.2089G>A)?

ABCA1 p.Ala697Thr (c.2089G>A) is associated with Tangier disease, hypoalphalipoproteinemia, primary, 1 (ClinVar).

How common is ABCA1 p.Ala697Thr (c.2089G>A) in the general population?

ABCA1 p.Ala697Thr (c.2089G>A) is rare (popmax 0.684%, afr) (gnomAD).

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.Ala697Thr (c.2089G>A)?

AlphaMissense predicts likely benign (score 0.195) — an in-silico prediction, not a clinical call.

ABCA1 p.Ala697Thr

c.2089G>A · rs114620717 · VCV364437

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.195 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.684%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Tangier disease

Computational evidence

Protein change
AlphaMissense	0.195	likely benign
REVEL	0.494	indeterminate
SaProt	LLR -5.84	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 4.1	GERP 2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 81 kb · p 0.081 · regional, not allelic
Overall
CADD	25.0	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 0.684% African / African-American · 513/74,994 alleles

Filtering AF 0.635% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.616%

Overall 0.0366% 590/1,614,086 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.684%	146
Admixed American	0.0433%	2,308
Remaining individualsnot grpmax-eligible	0.0432%	2,315
South Asian	0.00439%	22,769
European (non-Finnish)	0.00161%	62,106
Finnishnot grpmax-eligible	0.00156%	64,030

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.Ala697Thr
Coding: c.2089G>A
MANE Select: NM_005502
dbSNP: rs114620717
Type: single nucleotide variant
Location: chr9:104828942 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB
Residue 697: an α-helix

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 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-ala697thr (accessed [today's date]).

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