Is ABCB4 p.Val336fs (c.1006_1009del) pathogenic?

ABCB4 p.Val336fs (c.10061009del) is classified Likely pathogenic in ABCB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-17). Very rare (popmax 8.5e-05%, nfe); Associated with ABCB4-related disorder.

What condition is associated with ABCB4 p.Val336fs (c.1006_1009del)?

ABCB4 p.Val336fs (c.1006_1009del) is associated with ABCB4-related disorder (ClinVar).

How common is ABCB4 p.Val336fs (c.1006_1009del) in the general population?

ABCB4 p.Val336fs (c.1006_1009del) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

ABCB4 p.Val336fs

c.1006_1009del · VCV4896507

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Conditions

ABCB4-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 10 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.5e-05% European (non-Finnish) · 1/1,177,132 alleles

Overall 6.91e-05% 1/1,446,498 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: ABCB4
Protein: p.Val336fs
Coding: c.1006_1009del
MANE Select: NM_000443
Type: Deletion
Location: chr7:87444972 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 336: an α-helix; the abc transmembrane type-1 1 domain

Full ABCB4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ABCB4-related disorder

Similar variants

ABCB4 p.Ser339fs Pathogenic/Likely pathogenic ★★ same condition
ABCB4 p.Arg469fs Likely pathogenic ★ same condition
ABCB4 p.Val336Ala Uncertain significance ★ ⚠ same residue
ABCB4 p.Val336Asp Uncertain significance ★ ⚠ same residue
ABCB4 p.Val548fs Likely pathogenic same condition
ABCB4 p.Ile848del Uncertain significance same condition
ABCB4 c.2211+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCB4 c.286+1G>A 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/abcb4-p-val336fs (accessed [today's date]).

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