Is ABCB11 p.Asp29del (c.85_87del) pathogenic?

ABCB11 p.Asp29del (c.8587del) is classified Uncertain significance in ABCB11 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-04-14). Ultra-rare (popmax 0.0743%, sas); Associated with familial intrahepatic cholestasis.

What condition is associated with ABCB11 p.Asp29del (c.85_87del)?

ABCB11 p.Asp29del (c.85_87del) is associated with familial intrahepatic cholestasis (ClinVar).

How common is ABCB11 p.Asp29del (c.85_87del) in the general population?

ABCB11 p.Asp29del (c.85_87del) is ultra-rare (popmax 0.0743%, sas) (gnomAD).

ABCB11 p.Asp29del

c.85_87del · rs748922246 · VCV499999

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0743%, sas)

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 · substitutions only
Constraint at this position
Conservation	phyloP 5	GERP 0.71, phastCons 1
Overall
CADD	14.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0743% South Asian · 65/87,452 alleles

Filtering AF 0.0598% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0545%

Overall 0.00809% 129/1,594,838 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0743%	1,345
Remaining individualsnot grpmax-eligible	0.0146%	6,864
Admixed American	0.0121%	8,256
European (non-Finnish)	0.0041%	24,365

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.Asp29del
Coding: c.85_87del
MANE Select: NM_003742
dbSNP: rs748922246
Type: Deletion
Location: chr2:169016789 (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 29: the 'disordered' region

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 c.3213+1del Pathogenic ★★ same condition
ABCB11 p.Arg830fs Pathogenic ★★ same condition
ABCB11 p.Asn199fs Pathogenic/Likely pathogenic ★★ same condition
ABCB11 p.Asp848fs Pathogenic/Likely pathogenic ★★ same condition
ABCB11 p.Gln1058fs Pathogenic ★★ same condition
ABCB11 p.Gly1267fs Likely pathogenic ★★ same condition
ABCB11 p.Gly648fs Pathogenic ★★ same condition
ABCB11 p.Ile1061fs 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-asp29del (accessed [today's date]).

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