Is ABCA1 p.Ser296Thr (c.886T>A) pathogenic?

ABCA1 p.Ser296Thr (c.886T>A) is classified Conflicting classifications of pathogenicity in ABCA1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-09). AlphaMissense: likely benign (0.0873); Ultra-rare (popmax 0.0624%, eas); Associated with Cardiovascular phenotype.

What condition is associated with ABCA1 p.Ser296Thr (c.886T>A)?

ABCA1 p.Ser296Thr (c.886T>A) is associated with Cardiovascular phenotype (ClinVar).

How common is ABCA1 p.Ser296Thr (c.886T>A) in the general population?

ABCA1 p.Ser296Thr (c.886T>A) is ultra-rare (popmax 0.0624%, eas) (gnomAD).

What do computational predictors say about ABCA1 p.Ser296Thr (c.886T>A)?

AlphaMissense predicts likely benign (score 0.0873) — an in-silico prediction, not a clinical call.

ABCA1 p.Ser296Thr

c.886T>A · rs377673145 · VCV2186667

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0873 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0624%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0873	likely benign
REVEL	0.387	indeterminate
SaProt	LLR -7.02	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 9.2	GERP 1.2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 81 kb · p 0.081 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0624% East Asian · 28/44,862 alleles

Filtering AF 0.0443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0382%

Overall 0.00415% 67/1,614,062 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0624%	1,602
Remaining individualsnot grpmax-eligible	0.0256%	3,907
South Asian	0.0209%	4,794
Admixed American	0.00167%	60,018
European (non-Finnish)	0.000254%	393,343

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.Ser296Thr
Coding: c.886T>A
MANE Select: NM_005502
dbSNP: rs377673145
Type: single nucleotide variant
Location: chr9:104840447 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB
Residue 296: a disulfide bond

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-ser296thr (accessed [today's date]).

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