Is ABCB11 p.Glu395= (c.1185G>A) pathogenic?

ABCB11 p.Glu395= (c.1185G>A) is classified Benign in ABCB11 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-04-14). Common (popmax 5.53%, afr) — too common for a highly-penetrant pathogenic allele; Associated with familial intrahepatic cholestasis.

What condition is associated with ABCB11 p.Glu395= (c.1185G>A)?

ABCB11 p.Glu395= (c.1185G>A) is associated with familial intrahepatic cholestasis, progressive familial intrahepatic cholestasis type 2 (ClinVar).

ABCB11 p.Glu395=

Q: How common is ABCB11 p.Glu395= (c.1185G>A) in the general population?

ABCB11 p.Glu395= (c.1185G>A) is common (popmax 5.53%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1185G>A · rs57509552 · VCV259144

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 5.53%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

familial intrahepatic cholestasis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.15	GERP -0.67, phastCons 0.95
Overall
CADD	6.634	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.53% African / African-American · 4,078/73,698 alleles

Filtering AF 5.39% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.33%

Overall 0.295% 4,652/1,578,554 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.53%	18
Remaining individualsnot grpmax-eligible	0.433%	231
Admixed American	0.402%	249
Middle Eastern	0.238%	421
South Asian	0.0133%	7,533
European (non-Finnish)	0.0044%	22,705

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.Glu395=
Coding: c.1185G>A
MANE Select: NM_003742
dbSNP: rs57509552
Type: single nucleotide variant
Location: chr2:168979878 (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 395: an α-helix

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

Also linked: progressive familial intrahepatic cholestasis type 2

Similar variants

ABCB11 p.Glu395Asp Uncertain significance ★★ ⚠ 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
ABCB11 c.150+3A>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-glu395 (accessed [today's date]).

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