Is ABCB11 p.Ala804= (c.2412A>G) pathogenic?

ABCB11 p.Ala804= (c.2412A>G) is classified Benign in ABCB11 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-04-14). Common (popmax 8.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with familial intrahepatic cholestasis.

What condition is associated with ABCB11 p.Ala804= (c.2412A>G)?

ABCB11 p.Ala804= (c.2412A>G) is associated with familial intrahepatic cholestasis, progressive familial intrahepatic cholestasis type 2 (ClinVar).

ABCB11 p.Ala804=

Q: How common is ABCB11 p.Ala804= (c.2412A>G) in the general population?

ABCB11 p.Ala804= (c.2412A>G) is common (popmax 8.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2412A>G · rs11568373 · VCV259149

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 8.4%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

familial intrahepatic cholestasis

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 0.023	GERP -4
Overall
CADD	7.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.4% African / African-American · 6,223/74,100 alleles

Filtering AF 8.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.15%

Overall 0.457% 7,223/1,580,266 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.4%	12
Admixed American	0.754%	133
Remaining individualsnot grpmax-eligible	0.702%	142
Middle Eastern	0.25%	400
South Asian	0.0196%	5,108
European (non-Finnish)	0.0102%	9,760

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: ABCB11
Protein: p.Ala804=
Coding: c.2412A>G
MANE Select: NM_003742
dbSNP: rs11568373
Type: single nucleotide variant
Location: chr2:168944893 (GRCh38)
Gene constraint: LOEUF 0.739 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.23 · 9 PDB
Residue 804: an α-helix; the abc transmembrane type-1 2 domain

Full ABCB11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial intrahepatic cholestasis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: progressive familial intrahepatic cholestasis type 2

Similar variants

ABCB11 c.1084-2A>G Pathogenic ★★ same condition
ABCB11 c.1197+1G>T Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.1198-1G>C Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.1198-2A>C Likely pathogenic ★★ same condition
ABCB11 c.1435-2A>T Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.150+2T>C Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.150+3A>C Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.1638+1G>C Likely pathogenic ★★ 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/abcb11-p-ala804 (accessed [today's date]).

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