Is ABCA1 p.Ile680= (c.2040C>A) pathogenic?

ABCA1 p.Ile680= (c.2040C>A) is classified Benign in ABCA1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 66.4%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with ABCA1 p.Ile680= (c.2040C>A)?

ABCA1 p.Ile680= (c.2040C>A) is associated with Cardiovascular phenotype, Tangier disease, hypoalphalipoproteinemia, primary, 1 (ClinVar).

ABCA1 p.Ile680=

Q: How common is ABCA1 p.Ile680= (c.2040C>A) in the general population?

ABCA1 p.Ile680= (c.2040C>A) is common (popmax 66.4%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2040C>A · rs2853579 · VCV364438

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 66.4%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

Cardiovascular phenotype

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 3.5	GERP 2.1, phastCons 1
Overall
CADD	9.188	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 66.4% East Asian · 29,795/44,846 alleles

Filtering AF 65.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 65.5%

Overall 15.8% 255,126/1,613,864 alleles · common exomes 219,317/1,461,840 · genomes 35,809/152,024 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	66.4%	2
African / African-American	43.8%	2
Admixed American	20.9%	5
Middle Eastern	18.6%	5
Remaining individualsnot grpmax-eligible	18.2%	5
Ashkenazi Jewishnot grpmax-eligible	17.6%	6
South Asian	14.8%	7
European (non-Finnish)	12%	8
Finnishnot grpmax-eligible	10.4%	10
Amishnot grpmax-eligible	9.21%	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.Ile680=
Coding: c.2040C>A
MANE Select: NM_005502
dbSNP: rs2853579
Type: single nucleotide variant
Location: chr9:104828991 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB
Residue 680: an α-helix

Full ABCA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Tangier disease hypoalphalipoproteinemia, primary, 1

Similar variants

ABCA1 c.4175+1G>T Pathogenic/Likely pathogenic ★★ same condition
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 p.Thr940Met Pathogenic/Likely pathogenic ★★ same condition
ABCA1 c.3787+5C>A Uncertain significance ★★ same condition
ABCA1 c.*2330A>T 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-ile680 (accessed [today's date]).

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