Is ABCB11 p.Ala1283= (c.3849G>A) pathogenic?

ABCB11 p.Ala1283= (c.3849G>A) is classified Likely benign in ABCB11 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-14). Ultra-rare (popmax 0.0959%, eas); Associated with familial intrahepatic cholestasis.

What condition is associated with ABCB11 p.Ala1283= (c.3849G>A)?

ABCB11 p.Ala1283= (c.3849G>A) is associated with familial intrahepatic cholestasis (ClinVar).

How common is ABCB11 p.Ala1283= (c.3849G>A) in the general population?

ABCB11 p.Ala1283= (c.3849G>A) is ultra-rare (popmax 0.0959%, eas) (gnomAD).

ABCB11 p.Ala1283=

c.3849G>A · rs566857672 · VCV763177

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0959%, eas)

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 -9.8	GERP -4.2
Overall
CADD	0.687	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0959% East Asian · 43/44,858 alleles

Filtering AF 0.0731% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0651%

Overall 0.00991% 160/1,613,800 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0959%	1,043
Middle Eastern	0.033%	3,031
South Asian	0.011%	9,107
Admixed American	0.01%	9,999
Remaining individualsnot grpmax-eligible	0.008%	12,497
European (non-Finnish)	0.0078%	12,825
African / African-American	0.00267%	37,486

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.Ala1283=
Coding: c.3849G>A
MANE Select: NM_003742
dbSNP: rs566857672
Type: single nucleotide variant
Location: chr2:168923739 (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 1283: a turn; the abc transporter 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

Similar variants

ABCB11 p.Ala1283Val Uncertain significance ★★ ⚠ same residue
ABCB11 p.Ala1283Ser Uncertain significance ★ ⚠ same residue
ABCB11 p.Ala1283Thr Uncertain significance ★★ ⚠ same residue
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.1435-2A>T Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.150+3A>C Pathogenic/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-ala1283 (accessed [today's date]).

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