Is ABCB11 p.Pro103Ser (c.307C>T) pathogenic?

ABCB11 p.Pro103Ser (c.307C>T) is classified Pathogenic in ABCB11 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-01). AlphaMissense: likely benign (0.1219); Absent from gnomAD v4.1; Associated with progressive familial intrahepatic cholestasis type 2.

What condition is associated with ABCB11 p.Pro103Ser (c.307C>T)?

ABCB11 p.Pro103Ser (c.307C>T) is associated with progressive familial intrahepatic cholestasis type 2 (ClinVar).

How common is ABCB11 p.Pro103Ser (c.307C>T) in the general population?

ABCB11 p.Pro103Ser (c.307C>T) is absent from gnomAD v4.1 (gnomAD).

How is Progressive familial intrahepatic cholestasis inherited?

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

What do computational predictors say about ABCB11 p.Pro103Ser (c.307C>T)?

AlphaMissense predicts likely benign (score 0.1219) — an in-silico prediction, not a clinical call.

ABCB11 p.Pro103Ser

c.307C>T · rs2545484771 · VCV2687803

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1219 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

progressive familial intrahepatic cholestasis type 2

Computational evidence

Protein change
AlphaMissense	0.1219	likely benign ⚠ discordant with ClinVar
REVEL	0.384	indeterminate
SaProt	LLR -10.38	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.9, phastCons 1
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCB11
Protein: p.Pro103Ser
Coding: c.307C>T
MANE Select: NM_003742
dbSNP: rs2545484771
Type: single nucleotide variant
Location: chr2:169013354 (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 103: the abc transmembrane type-1 1 domain

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

For Progressive familial intrahepatic cholestasis (Orphanet):

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

Similar variants

ABCB11 p.Pro103= Likely benign ★ same residue
ABCB11 c.1084-2A>G Pathogenic ★★ same condition
ABCB11 c.1198-1G>C Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.1198-2A>C 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
ABCB11 c.1810-1G>A 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-pro103ser (accessed [today's date]).

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