Is ABCA1 p.Leu2012Val (c.6034C>G) pathogenic?

ABCA1 p.Leu2012Val (c.6034C>G) is classified Uncertain significance in ABCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-16). AlphaMissense: likely benign (0.1105); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with ABCA1 p.Leu2012Val (c.6034C>G)?

ABCA1 p.Leu2012Val (c.6034C>G) is associated with Cardiovascular phenotype (ClinVar).

How common is ABCA1 p.Leu2012Val (c.6034C>G) in the general population?

ABCA1 p.Leu2012Val (c.6034C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCA1 p.Leu2012Val (c.6034C>G)?

AlphaMissense predicts likely benign (score 0.1105) — an in-silico prediction, not a clinical call.

ABCA1 p.Leu2012Val

c.6034C>G · rs2538038298 · VCV2299205

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1105 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1105	likely benign
REVEL	0.401	indeterminate
SaProt	LLR -8.29	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 12	GERP 2, 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

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Leu2012Val
Coding: c.6034C>G
MANE Select: NM_005502
dbSNP: rs2538038298
Type: single nucleotide variant
Location: chr9:104788461 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB
Residue 2012: the abc transporter 2 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-leu2012val (accessed [today's date]).

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