Is ABCG8 p.Ala296= (c.888G>T) pathogenic?

ABCG8 p.Ala296= (c.888G>T) is classified Conflicting classifications of pathogenicity in ABCG8 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-10). Rare (popmax 0.124%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ABCG8 p.Ala296= (c.888G>T)?

ABCG8 p.Ala296= (c.888G>T) is associated with Cardiovascular phenotype (ClinVar).

How common is ABCG8 p.Ala296= (c.888G>T) in the general population?

ABCG8 p.Ala296= (c.888G>T) is rare (popmax 0.124%, afr) (gnomAD).

ABCG8 p.Ala296=

c.888G>T · rs143182625 · VCV501912

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.124%, 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 -7.1	GERP -3.5
Overall
CADD	0.029	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.124% African / African-American · 93/74,992 alleles

Filtering AF 0.104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0961%

Overall 0.00657% 106/1,614,070 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.124%	806
Middle Eastern	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.0096%	10,418
Admixed American	0.00833%	12,003
European (non-Finnish)	8.47e-05%	1,180,022

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: ABCG8
Protein: p.Ala296=
Coding: c.888G>T
MANE Select: NM_022437
dbSNP: rs143182625
Type: single nucleotide variant
Location: chr2:43852792 (GRCh38)
Gene constraint: LOEUF 1.329 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.94 · 8 PDB
Residue 296: the abc transporter domain; a β-strand

Full ABCG8 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

ABCG8 p.Ala296Val Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCG8 p.Arg121Ter Pathogenic ★★ same condition
ABCG8 p.Arg405Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABCG8 p.Gln271Ter Pathogenic/Likely pathogenic ★★ same condition
ABCG8 p.Ala248Thr Uncertain significance ★★ ⚠ same condition
ABCG8 p.Ala346Thr Uncertain significance ★★ ⚠ same condition
ABCG8 p.Ala449Val Uncertain significance ★★ ⚠ same condition
ABCG8 p.Ala450Thr 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/abcg8-p-ala296 (accessed [today's date]).

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