Is ABCA1 p.Arg666= (c.1998G>A) pathogenic?

ABCA1 p.Arg666= (c.1998G>A) is classified Likely benign in ABCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-31). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with ABCA1 p.Arg666= (c.1998G>A)?

ABCA1 p.Arg666= (c.1998G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is ABCA1 p.Arg666= (c.1998G>A) in the general population?

ABCA1 p.Arg666= (c.1998G>A) is absent from gnomAD v4.1 (gnomAD).

ABCA1 p.Arg666=

c.1998G>A · rs2538170234 · VCV3224731

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -0.67	GERP 2.1, phastCons 0.009
Overall
CADD	8.812	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCA1
Protein: p.Arg666=
Coding: c.1998G>A
MANE Select: NM_005502
dbSNP: rs2538170234
Type: single nucleotide variant
Location: chr9:104829033 (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

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

Similar variants

ABCA1 p.Arg666Gln Conflicting classifications of pathogenicity ★ same residue
ABCA1 p.Arg666Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCA1 c.4175+1G>T Pathogenic/Likely pathogenic ★★ same condition
ABCA1 p.Thr940Met Pathogenic/Likely pathogenic ★★ same condition
ABCA1 c.3787+5C>A Uncertain significance ★★ same condition
ABCA1 p.Ala1855Ser Uncertain significance ★★ ⚠ same condition
ABCA1 p.Ala766Ser Uncertain significance ★★ ⚠ same condition
ABCA1 p.Arg1283Cys 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-arg666 (accessed [today's date]).

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