Is ABCA1 p.Thr956= (c.2868C>T) pathogenic?

ABCA1 p.Thr956= (c.2868C>T) is classified Benign/Likely benign in ABCA1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-28). Low-frequency (popmax 3.62%, afr); Associated with hypoalphalipoproteinemia, primary, 1.

What condition is associated with ABCA1 p.Thr956= (c.2868C>T)?

ABCA1 p.Thr956= (c.2868C>T) is associated with hypoalphalipoproteinemia, primary, 1, Tangier disease (ClinVar).

How common is ABCA1 p.Thr956= (c.2868C>T) in the general population?

ABCA1 p.Thr956= (c.2868C>T) is low-frequency (popmax 3.62%, afr) (gnomAD).

How is Apolipoprotein A-I deficiency inherited?

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

ABCA1 p.Thr956=

c.2868C>T · rs35561837 · VCV496292

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.62%, afr)

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 -3	GERP -4.2
Overall
CADD	1.024	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.62% African / African-American · 2,716/75,010 alleles

Filtering AF 3.51% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.46%

Overall 0.197% 3,173/1,614,024 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.62%	28
Middle Eastern	0.285%	351
Remaining individualsnot grpmax-eligible	0.278%	359
Admixed American	0.24%	417
South Asian	0.0143%	7,006
European (non-Finnish)	0.00898%	11,132
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,802
Finnishnot grpmax-eligible	0.00156%	64,034

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.Thr956=
Coding: c.2868C>T
MANE Select: NM_005502
dbSNP: rs35561837
Type: single nucleotide variant
Location: chr9:104821467 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB
Residue 956: the abc transporter 1 domain; a β-strand

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-thr956 (accessed [today's date]).

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