Is ABCA1 p.Ser545= (c.1635C>T) pathogenic?

ABCA1 p.Ser545= (c.1635C>T) is classified Benign/Likely benign in ABCA1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-27). Low-frequency (popmax 2.71%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ABCA1 p.Ser545= (c.1635C>T)?

ABCA1 p.Ser545= (c.1635C>T) is associated with Cardiovascular phenotype, Tangier disease, hypoalphalipoproteinemia, primary, 1 (ClinVar).

How common is ABCA1 p.Ser545= (c.1635C>T) in the general population?

ABCA1 p.Ser545= (c.1635C>T) is low-frequency (popmax 2.71%, afr) (gnomAD).

ABCA1 p.Ser545=

c.1635C>T · rs9282539 · VCV364443

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.71%, afr)

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 -1.5	GERP -1.4
Overall
CADD	4.511	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.71% African / African-American · 2,036/75,024 alleles

Filtering AF 2.62% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.58%

Overall 0.153% 2,477/1,614,188 alleles · low-frequency exomes 1,252/1,461,880 · genomes 1,225/152,308 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.71%	37
Admixed American	0.235%	426
Remaining individualsnot grpmax-eligible	0.234%	428
Middle Eastern	0.132%	758
European (non-Finnish)	0.0117%	8,551
South Asian	0.00878%	11,386

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.Ser545=
Coding: c.1635C>T
MANE Select: NM_005502
dbSNP: rs9282539
Type: single nucleotide variant
Location: chr9:104831702 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB
Residue 545: 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 p.Ser545Asn Likely benign ★★ same residue
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

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-ser545 (accessed [today's date]).

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