Is ABCB11 p.Phe334Val (c.1000T>G) pathogenic?

ABCB11 p.Phe334Val (c.1000T>G) is classified Uncertain significance in ABCB11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-09). AlphaMissense: likely pathogenic (0.7954); Absent from gnomAD v4.1; Associated with ABCB11-related disorder.

What condition is associated with ABCB11 p.Phe334Val (c.1000T>G)?

ABCB11 p.Phe334Val (c.1000T>G) is associated with ABCB11-related disorder (ClinVar).

How common is ABCB11 p.Phe334Val (c.1000T>G) in the general population?

ABCB11 p.Phe334Val (c.1000T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCB11 p.Phe334Val (c.1000T>G)?

AlphaMissense predicts likely pathogenic (score 0.7954) — an in-silico prediction, not a clinical call.

ABCB11 p.Phe334Val

c.1000T>G · rs2545431828 · VCV2632886

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7954 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABCB11-related disorder

Computational evidence

Protein change
AlphaMissense	0.7954	likely pathogenic
REVEL	0.898	moderately pathogenic-leaning
SaProt	LLR -12.08	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 2.1, phastCons 1
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCB11
Protein: p.Phe334Val
Coding: c.1000T>G
MANE Select: NM_003742
dbSNP: rs2545431828
Type: single nucleotide variant
Location: chr2:168986193 (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 334: 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

ABCB11-related disorder

Similar variants

ABCB11 c.611+1G>A Pathogenic ★★ same condition
ABCB11 c.909-1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCB11 p.Arg1050Cys Pathogenic ★★ ⚠ same condition
ABCB11 p.Arg1057Ter Pathogenic ★★ same condition
ABCB11 p.Arg1235Ter Pathogenic/Likely pathogenic ★★ same condition
ABCB11 p.Arg487His Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABCB11 p.Gln794Ter Pathogenic ★★ same condition
ABCB11 p.Glu297Gly 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-phe334val (accessed [today's date]).

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