Is ABCA1 p.Leu2068= (c.6204G>C) pathogenic?

ABCA1 p.Leu2068= (c.6204G>C) is classified Uncertain significance in ABCA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-18). Very rare (popmax 0.00195%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with ABCA1 p.Leu2068= (c.6204G>C)?

ABCA1 p.Leu2068= (c.6204G>C) is associated with Cardiovascular phenotype (ClinVar).

How common is ABCA1 p.Leu2068= (c.6204G>C) in the general population?

ABCA1 p.Leu2068= (c.6204G>C) is very rare (popmax 0.00195%, nfe) (gnomAD).

ABCA1 p.Leu2068=

c.6204G>C · rs947401662 · VCV2159476

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00195%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Overall
CADD	19.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00195% European (non-Finnish) · 23/1,179,934 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00155% 25/1,613,904 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00195%	51,302
Remaining individualsnot grpmax-eligible	0.0016%	62,468
African / African-American	0.00133%	74,908

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.Leu2068=
Coding: c.6204G>C
MANE Select: NM_018376 · reported on NM_005502
dbSNP: rs947401662
Type: single nucleotide variant
Location: chr9:104787920 (GRCh38)

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

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-leu2068 (accessed [today's date]).

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