Is ABCB11 p.Val366= (c.1098C>T) pathogenic?

ABCB11 p.Val366= (c.1098C>T) is classified Likely benign in ABCB11 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-14). Ultra-rare (popmax 0.0134%, afr); Associated with familial intrahepatic cholestasis.

What condition is associated with ABCB11 p.Val366= (c.1098C>T)?

ABCB11 p.Val366= (c.1098C>T) is associated with familial intrahepatic cholestasis (ClinVar).

How common is ABCB11 p.Val366= (c.1098C>T) in the general population?

ABCB11 p.Val366= (c.1098C>T) is ultra-rare (popmax 0.0134%, afr) (gnomAD).

ABCB11 p.Val366=

c.1098C>T · rs565224768 · VCV1369921

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, afr)

Conditions

familial intrahepatic cholestasis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.2	GERP 0.35, phastCons 1
Overall
CADD	7.202	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% African / African-American · 10/74,766 alleles

Filtering AF 0.00724% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00551%

Overall 0.000686% 11/1,603,702 alleles · ultra-rare exomes 8/1,451,556 · genomes 3/152,146 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0134%	7,477
Remaining individualsnot grpmax-eligible	0.00161%	62,050

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.Val366=
Coding: c.1098C>T
MANE Select: NM_003742
dbSNP: rs565224768
Type: single nucleotide variant
Location: chr2:168979965 (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 366: an α-helix; the abc transmembrane type-1 1 domain

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.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.1435-2A>T 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.2012-2A>G 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-val366 (accessed [today's date]).

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