Is ABCA1 p.Glu992= (c.2976A>G) pathogenic?

ABCA1 p.Glu992= (c.2976A>G) is classified Likely benign in ABCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-31). Very rare (popmax 0.00133%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ABCA1 p.Glu992= (c.2976A>G)?

ABCA1 p.Glu992= (c.2976A>G) is associated with Cardiovascular phenotype (ClinVar).

How common is ABCA1 p.Glu992= (c.2976A>G) in the general population?

ABCA1 p.Glu992= (c.2976A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

ABCA1 p.Glu992=

c.2976A>G · rs1384274571 · VCV2454043

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.3	GERP -4
Overall
CADD	5.897	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,920 alleles

Overall 6.2e-05% 1/1,614,050 alleles · very rare exomes 0/1,461,880 · genomes 1/152,170 · joint denominator

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.Glu992=
Coding: c.2976A>G
MANE Select: NM_005502
dbSNP: rs1384274571
Type: single nucleotide variant
Location: chr9:104820054 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB
Residue 992: the abc transporter 1 domain; 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

Similar variants

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
ABCA1 p.Arg1342Trp Uncertain significance ★★ ⚠ same condition
ABCA1 p.Arg1417Cys 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-glu992 (accessed [today's date]).

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