Is ABCB11 p.Ser901Arg (c.2703C>G) pathogenic?

ABCB11 p.Ser901Arg (c.2703C>G) is classified Likely pathogenic in ABCB11 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-14). AlphaMissense: likely pathogenic (0.9959); Very rare (popmax 0.00223%, eas); Associated with progressive familial intrahepatic cholestasis type 2.

How common is ABCB11 p.Ser901Arg (c.2703C>G) in the general population?

ABCB11 p.Ser901Arg (c.2703C>G) is very rare (popmax 0.00223%, eas) (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.Ser901Arg (c.2703C>G)?

AlphaMissense predicts likely pathogenic (score 0.9959) — an in-silico prediction, not a clinical call.

ABCB11 p.Ser901Arg

Q: What condition is associated with ABCB11 p.Ser901Arg (c.2703C>G)?

ABCB11 p.Ser901Arg (c.2703C>G) is associated with progressive familial intrahepatic cholestasis type 2, familial intrahepatic cholestasis (ClinVar).

c.2703C>G · VCV3776846

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9959 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

progressive familial intrahepatic cholestasis type 2

Computational evidence

Protein change
AlphaMissense	0.9959	likely pathogenic ✓ concordant with ClinVar · top 1% in ABCB11
REVEL	0.752	pathogenic-leaning
SaProt	LLR -15.60	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP -0.78, phastCons 1
Overall
CADD	24.6	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

Grpmax group 0.00223% East Asian · 1/44,880 alleles

Overall 0.000124% 2/1,613,792 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,880
European (non-Finnish)	8.48e-05%	1,179,888

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.Ser901Arg
Coding: c.2703C>G
MANE Select: NM_003742
Type: single nucleotide variant
Location: chr2:168936341 (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 901: an α-helix; the abc transmembrane type-1 2 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

Also linked: familial intrahepatic cholestasis

For Progressive familial intrahepatic cholestasis (Orphanet):

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

Similar variants

ABCB11 p.Ser901Ile Likely pathogenic ★★ same residue
ABCB11 p.Ser901Asn Likely pathogenic ★ 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.1198-2A>C Likely pathogenic ★★ same condition
ABCB11 c.1435-2A>T Pathogenic/Likely pathogenic ★★ same condition
ABCB11 c.150+2T>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-ser901arg (accessed [today's date]).

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