Is ABCA1 p.Ser723= (c.2169C>T) pathogenic?

ABCA1 p.Ser723= (c.2169C>T) is classified Benign/Likely benign in ABCA1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.0154%, sas); Associated with Cardiovascular phenotype.

What condition is associated with ABCA1 p.Ser723= (c.2169C>T)?

ABCA1 p.Ser723= (c.2169C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is ABCA1 p.Ser723= (c.2169C>T) in the general population?

ABCA1 p.Ser723= (c.2169C>T) is ultra-rare (popmax 0.0154%, sas) (gnomAD).

ABCA1 p.Ser723=

c.2169C>T · rs143933174 · VCV1787035

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0154%, sas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP -10	GERP -4.2
Overall
CADD	1.371	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0154% South Asian · 14/91,086 alleles

Filtering AF 0.00919% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00735%

Overall 0.0356% 575/1,614,130 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.683%	147
Remaining individualsnot grpmax-eligible	0.0304%	3,290
South Asiangrpmax	0.0154%	6,506
European (non-Finnish)	0.00864%	11,569
Admixed American	0.00333%	30,002
African / African-American	0.00133%	75,030

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser723=
Coding: c.2169C>T
MANE Select: NM_005502
dbSNP: rs143933174
Type: single nucleotide variant
Location: chr9:104827116 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB
Residue 723: 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-ser723 (accessed [today's date]).

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