Is ABCB11 p.Arg299Ile (c.896_897delinsTT) pathogenic?

ABCB11 p.Arg299Ile (c.896897delinsTT) is classified Uncertain significance in ABCB11 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-04-14). Absent from gnomAD; Associated with progressive familial intrahepatic cholestasis type 2.

What condition is associated with ABCB11 p.Arg299Ile (c.896_897delinsTT)?

ABCB11 p.Arg299Ile (c.896_897delinsTT) is associated with progressive familial intrahepatic cholestasis type 2, familial intrahepatic cholestasis (ClinVar).

How common is ABCB11 p.Arg299Ile (c.896_897delinsTT) in the general population?

ABCB11 p.Arg299Ile (c.896_897delinsTT) is absent from gnomAD (gnomAD).

How is Progressive familial intrahepatic cholestasis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ABCB11 p.Arg299Ile

c.896_897delinsTT · rs2106004734 · VCV1310347

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

progressive familial intrahepatic cholestasis type 2

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 2.9	GERP -1.7, phastCons 1

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ABCB11
Protein: p.Arg299Ile
Coding: c.896_897delinsTT
MANE Select: NM_003742
dbSNP: rs2106004734
Type: Indel
Location: chr2:168990812 (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 299: an α-helix; the abc transmembrane type-1 1 domain; a UniProt-annotated variant site (in)

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

Disease context

progressive familial intrahepatic cholestasis type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial intrahepatic cholestasis

For Progressive familial intrahepatic cholestasis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood, Infancy, Neonatal

Similar variants

ABCB11 p.Arg299Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCB11 p.Lys1043fs Pathogenic ★★ same condition
ABCB11 c.2177_2178+1delinsGT Pathogenic ★ same condition
ABCB11 c.3213+1_3213+2delinsA Pathogenic ★ same condition
ABCB11 p.Leu241fs Pathogenic ★ same condition
ABCB11 p.Ser1154fs Pathogenic ★ same condition
ABCB11 p.Thr1121fs Pathogenic ★ same condition
ABCB11 p.Arg299Ser Uncertain significance ★ ⚠ same residue

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-arg299ile (accessed [today's date]).

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