Is ABCB11 p.Ser22Ter (c.65C>G) pathogenic?

ABCB11 p.Ser22Ter (c.65C>G) is classified Pathogenic/Likely pathogenic in ABCB11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-06-29). Very rare (popmax 0.00133%, afr); Associated with benign recurrent intrahepatic cholestasis type 2.

What condition is associated with ABCB11 p.Ser22Ter (c.65C>G)?

ABCB11 p.Ser22Ter (c.65C>G) is associated with benign recurrent intrahepatic cholestasis type 2 (ClinVar).

How common is ABCB11 p.Ser22Ter (c.65C>G) in the general population?

ABCB11 p.Ser22Ter (c.65C>G) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Benign recurrent intrahepatic cholestasis inherited?

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

ABCB11 p.Ser22Ter

c.65C>G · rs1695418522 · VCV2674704

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

benign recurrent intrahepatic cholestasis type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.3	GERP 1.9, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,984 alleles

Overall 6.85e-05% 1/1,460,890 alleles · very rare

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.Ser22Ter
Coding: c.65C>G
MANE Select: NM_003742
dbSNP: rs1695418522
Type: single nucleotide variant
Location: chr2:169018061 (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 22: the 'disordered' region

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

Disease context

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

For Benign recurrent intrahepatic cholestasis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages

Similar variants

ABCB11 p.Ser22= Likely benign ★ same residue
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+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.150+3A>C Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.2011+1G>T Likely pathogenic ★★ same condition
ABCB11 c.2012-8T>G 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-ser22ter (accessed [today's date]).

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