Is ABCA1 p.Gln1678= (c.5034G>A) pathogenic?

ABCA1 p.Gln1678= (c.5034G>A) is classified Benign/Likely benign in ABCA1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-09). Rare (popmax 0.59%, eas); Associated with Tangier disease.

What condition is associated with ABCA1 p.Gln1678= (c.5034G>A)?

ABCA1 p.Gln1678= (c.5034G>A) is associated with Tangier disease, hypoalphalipoproteinemia, primary, 1 (ClinVar).

How common is ABCA1 p.Gln1678= (c.5034G>A) in the general population?

ABCA1 p.Gln1678= (c.5034G>A) is rare (popmax 0.59%, eas) (gnomAD).

How is Tangier disease inherited?

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

ABCA1 p.Gln1678=

c.5034G>A · rs13306075 · VCV364395

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.59%, eas)

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 0.14	GERP 1.2, phastCons 0.94
Overall
CADD	8.091	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.59% East Asian · 265/44,880 alleles

Filtering AF 0.532% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.509%

Overall 0.0178% 288/1,614,126 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.59%	169
Remaining individualsnot grpmax-eligible	0.0272%	3,677
South Asian	0.00549%	18,214
European (non-Finnish)	8.47e-05%	1,180,027

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.Gln1678=
Coding: c.5034G>A
MANE Select: NM_005502
dbSNP: rs13306075
Type: single nucleotide variant
Location: chr9:104798508 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB
Residue 1678: 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-gln1678 (accessed [today's date]).

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