Is ABCB11 p.Asp36= (c.108T>C) pathogenic?

ABCB11 p.Asp36= (c.108T>C) is classified Benign in ABCB11 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-04-14). Common (popmax 28.3%, eas) — too common for a highly-penetrant pathogenic allele; Associated with familial intrahepatic cholestasis.

What condition is associated with ABCB11 p.Asp36= (c.108T>C)?

ABCB11 p.Asp36= (c.108T>C) is associated with familial intrahepatic cholestasis, progressive familial intrahepatic cholestasis type 2 (ClinVar).

ABCB11 p.Asp36=

Q: How common is ABCB11 p.Asp36= (c.108T>C) in the general population?

ABCB11 p.Asp36= (c.108T>C) is common (popmax 28.3%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.108T>C · rs3815675 · VCV259143

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 28.3%, eas) — 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 1.4	GERP -3.6, phastCons 0.59
Overall
CADD	6.443	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 28.3% East Asian · 12,664/44,804 alleles

Filtering AF 27.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 27.7%

Overall 1.18% 19,097/1,613,040 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	28.3%	4
Admixed American	4.61%	22
Remaining individualsnot grpmax-eligible	2.27%	44
South Asian	1.07%	93
Ashkenazi Jewishnot grpmax-eligible	0.953%	105
African / African-American	0.283%	354
Middle Eastern	0.215%	466
European (non-Finnish)	0.0628%	1,592
Finnishnot grpmax-eligible	0.036%	2,780

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.Asp36=
Coding: c.108T>C
MANE Select: NM_003742
dbSNP: rs3815675
Type: single nucleotide variant
Location: chr2:169014345 (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 36: the 'disordered' region

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.Asp36Gly Uncertain significance ⚠ same residue
ABCB11 p.Asp36Val 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

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-asp36 (accessed [today's date]).

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