Is ABCB11 p.Glu636Val (c.1907A>T) pathogenic?

ABCB11 p.Glu636Val (c.1907A>T) is classified Conflicting classifications of pathogenicity in ABCB11 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-04-14). AlphaMissense: likely pathogenic (0.9055); Very rare (popmax 0.00167%, amr); Associated with familial intrahepatic cholestasis.

What condition is associated with ABCB11 p.Glu636Val (c.1907A>T)?

ABCB11 p.Glu636Val (c.1907A>T) is associated with familial intrahepatic cholestasis (ClinVar).

How common is ABCB11 p.Glu636Val (c.1907A>T) in the general population?

ABCB11 p.Glu636Val (c.1907A>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ABCB11 p.Glu636Val (c.1907A>T)?

AlphaMissense predicts likely pathogenic (score 0.9055) — an in-silico prediction, not a clinical call.

ABCB11 p.Glu636Val

c.1907A>T · rs199671371 · VCV1974573

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9055 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial intrahepatic cholestasis

Computational evidence

Protein change
AlphaMissense	0.9055	likely pathogenic · top 10% in ABCB11
REVEL	0.903	moderately pathogenic-leaning
SaProt	LLR -15.83	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.39	donor gain · deltas
Pangolin	Δ0.41	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.8	GERP 2.1, phastCons 1
Overall
CADD	33.0	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 0.00167% Admixed American · 1/59,824 alleles

Overall 0.000658% 1/152,068 alleles · very rare

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.Glu636Val
Coding: c.1907A>T
MANE Select: NM_003742
dbSNP: rs199671371
Type: single nucleotide variant
Location: chr2:168969454 (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 636: a β-strand; the abc transporter 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 p.Glu636Gly Likely pathogenic ★★ same residue
ABCB11 p.Glu636Lys 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.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

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-glu636val (accessed [today's date]).

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