Is ABCA1 p.Thr1792= (c.5376C>T) pathogenic?

ABCA1 p.Thr1792= (c.5376C>T) is classified Conflicting classifications of pathogenicity in ABCA1 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-02-04). Rare (popmax 0.565%, mid); Associated with Tangier disease.

What condition is associated with ABCA1 p.Thr1792= (c.5376C>T)?

ABCA1 p.Thr1792= (c.5376C>T) is associated with Tangier disease, hypoalphalipoproteinemia, primary, 1 (ClinVar).

How common is ABCA1 p.Thr1792= (c.5376C>T) in the general population?

ABCA1 p.Thr1792= (c.5376C>T) is rare (popmax 0.565%, mid) (gnomAD).

How is Tangier disease inherited?

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

ABCA1 p.Thr1792=

c.5376C>T · rs13306077 · VCV364392

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.565%, mid)

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 -0.66	GERP 1.2
Overall
CADD	3.047	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.565% Middle Eastern · 27/4,780 alleles

Filtering AF 0.399% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.343%

Overall 0.242% 3,901/1,612,566 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.86%	54
Middle Easterngrpmax	0.565%	177
Ashkenazi Jewishnot grpmax-eligible	0.459%	218
Admixed American	0.285%	351
European (non-Finnish)	0.272%	368
Remaining individualsnot grpmax-eligible	0.255%	392
South Asian	0.142%	706
East Asian	0.0513%	1,951
African / African-American	0.04%	2,500
Finnishnot grpmax-eligible	0.00312%	32,012

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr1792=
Coding: c.5376C>T
MANE Select: NM_005502
dbSNP: rs13306077
Type: single nucleotide variant
Location: chr9:104796059 (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.Thr1792Ala 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
ABCA1 c.*379C>T Uncertain significance ★★ same condition
ABCA1 p.Arg126Cys 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-thr1792 (accessed [today's date]).

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