Is ABCA1 p.Arg1925Gln (c.5774G>A) pathogenic?

ABCA1 p.Arg1925Gln (c.5774G>A) is classified Conflicting classifications of pathogenicity in ABCA1 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.0782); Rare (popmax 0.151%, nfe); Associated with Tangier disease.

What condition is associated with ABCA1 p.Arg1925Gln (c.5774G>A)?

ABCA1 p.Arg1925Gln (c.5774G>A) is associated with Tangier disease, hypoalphalipoproteinemia, primary, 1 (ClinVar).

How common is ABCA1 p.Arg1925Gln (c.5774G>A) in the general population?

ABCA1 p.Arg1925Gln (c.5774G>A) is rare (popmax 0.151%, nfe) (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.Arg1925Gln (c.5774G>A)?

AlphaMissense predicts likely benign (score 0.0782) — an in-silico prediction, not a clinical call.

ABCA1 p.Arg1925Gln

c.5774G>A · rs142688906 · VCV364385

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0782 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.151%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Tangier disease

Computational evidence

Protein change
AlphaMissense	0.0782	likely benign
REVEL	0.436	indeterminate
SaProt	LLR -6.44	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	GERP 2.1, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 22 kb · p 3.8e-10 · regional, not allelic
Overall
CADD	22.4	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 0.151% European (non-Finnish) · 1,778/1,179,754 alleles

Filtering AF 0.145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.142%

Overall 0.16% 2,585/1,613,370 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.06%	94
European (non-Finnish)grpmax	0.151%	664
Remaining individualsnot grpmax-eligible	0.106%	947
Ashkenazi Jewishnot grpmax-eligible	0.0912%	1,096
Middle Eastern	0.033%	3,030
Admixed American	0.0317%	3,158
African / African-American	0.0147%	6,820
South Asian	0.00659%	15,174
East Asian	0.00223%	44,826

Finnish 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.Arg1925Gln
Coding: c.5774G>A
MANE Select: NM_005502
dbSNP: rs142688906
Type: single nucleotide variant
Location: chr9:104791982 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB
Residue 1925: a UniProt-annotated variant site (in scott syndrome; shows impaired trafficking of the mutant protein to the plasma membrane); the abc transporter 2 domain

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.Arg1925Trp 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-arg1925gln (accessed [today's date]).

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