Is ABCA1 p.Ile883Met (c.2649A>G) pathogenic?

ABCA1 p.Ile883Met (c.2649A>G) is classified Benign in ABCA1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0632); Common (popmax 66.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with hypoalphalipoproteinemia, primary, 1.

What condition is associated with ABCA1 p.Ile883Met (c.2649A>G)?

ABCA1 p.Ile883Met (c.2649A>G) is associated with hypoalphalipoproteinemia, primary, 1, Tangier disease (ClinVar).

How is Apolipoprotein A-I deficiency inherited?

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

What do computational predictors say about ABCA1 p.Ile883Met (c.2649A>G)?

AlphaMissense predicts likely benign (score 0.0632) — an in-silico prediction, not a clinical call.

ABCA1 p.Ile883Met

Q: How common is ABCA1 p.Ile883Met (c.2649A>G) in the general population?

ABCA1 p.Ile883Met (c.2649A>G) is common (popmax 66.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2649A>G · rs2066714 · VCV364426

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0632 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 66.7%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypoalphalipoproteinemia, primary, 1

Computational evidence

Protein change
AlphaMissense	0.0632	likely benign
REVEL	0.156	moderately benign-leaning
SaProt	LLR -6.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -2.8
Regional constraint	o/e 0.95	unconstrained · MANE · 81 kb · p 0.081 · regional, not allelic
Overall
CADD	0.791	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 66.7% East Asian · 29,905/44,844 alleles

Filtering AF 66.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 65.8%

Overall 16.7% 269,624/1,613,862 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	66.7%	1
African / African-American	48.4%	2
Admixed American	22.2%	5
Middle Eastern	20.8%	5
Ashkenazi Jewishnot grpmax-eligible	19.7%	5
Remaining individualsnot grpmax-eligible	19.5%	5
South Asian	14.9%	7
European (non-Finnish)	12.8%	8
Finnishnot grpmax-eligible	9.84%	10
Amishnot grpmax-eligible	9.23%	11

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.Ile883Met
Coding: c.2649A>G
MANE Select: NM_005502
dbSNP: rs2066714
Type: single nucleotide variant
Location: chr9:104824472 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB
Residue 883: a UniProt-annotated variant site (in)

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 p.Ile883Val Likely benign ★ 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-ile883met (accessed [today's date]).

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