Is ABCB11 p.Val444Asp (c.1331T>A) pathogenic?

ABCB11 p.Val444Asp (c.1331T>A) is classified Uncertain significance in ABCB11 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-14). AlphaMissense: likely benign (0.165); Absent from gnomAD v4.1; Associated with familial intrahepatic cholestasis.

What condition is associated with ABCB11 p.Val444Asp (c.1331T>A)?

ABCB11 p.Val444Asp (c.1331T>A) is associated with familial intrahepatic cholestasis (ClinVar).

How common is ABCB11 p.Val444Asp (c.1331T>A) in the general population?

ABCB11 p.Val444Asp (c.1331T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCB11 p.Val444Asp (c.1331T>A)?

AlphaMissense predicts likely benign (score 0.165) — an in-silico prediction, not a clinical call.

ABCB11 p.Val444Asp

c.1331T>A · VCV4846203

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.165 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,611,282)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

familial intrahepatic cholestasis

Computational evidence

Protein change
AlphaMissense	0.165	likely benign
REVEL	0.415	indeterminate
SaProt	LLR -10.99	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 0.89, phastCons 0.96
Overall
CADD	22.3	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

No allele count reported in gnomAD v4.1 (AN 1,611,282). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ABCB11
Protein: p.Val444Asp
Coding: c.1331T>A
MANE Select: NM_003742
Type: single nucleotide variant
Location: chr2:168973818 (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 444: the abc transporter 1 domain; a UniProt-annotated variant site (does not affect transport capacity for taurocholate; increases transport activity of taurocholate in a low cholesterol environment; increases transport activity of taurocholate in a high cholesterol environment; does not affect cell surface protein expression; does not affect protein expression); a UniProt-annotated variant site (in)

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.Val444Ala Benign ★★ ⚠ same residue
ABCB11 p.Val444Gly 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.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-val444asp (accessed [today's date]).

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