Is ABCA1 p.Asp1398= (c.4194C>T) pathogenic?

ABCA1 p.Asp1398= (c.4194C>T) is classified Conflicting classifications of pathogenicity in ABCA1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-07-18). Very rare (popmax 0.00678%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with ABCA1 p.Asp1398= (c.4194C>T)?

ABCA1 p.Asp1398= (c.4194C>T) is associated with Cardiovascular phenotype, Tangier disease, hypoalphalipoproteinemia, primary, 1 (ClinVar).

How common is ABCA1 p.Asp1398= (c.4194C>T) in the general population?

ABCA1 p.Asp1398= (c.4194C>T) is very rare (popmax 0.00678%, nfe) (gnomAD).

ABCA1 p.Asp1398=

c.4194C>T · rs752528416 · VCV913220

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00678%, nfe)

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 -1.8	GERP -4
Overall
CADD	0.31	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00678% European (non-Finnish) · 80/1,180,028 alleles

Filtering AF 0.00554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00514%

Overall 0.00508% 82/1,614,054 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00678%	14,750
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
African / African-American	0.00133%	74,932

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.Asp1398=
Coding: c.4194C>T
MANE Select: NM_005502
dbSNP: rs752528416
Type: single nucleotide variant
Location: chr9:104809546 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB
Residue 1398: a β-strand

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-asp1398 (accessed [today's date]).

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