Is ABCB4 p.Arg469fs (c.1406_1409del) pathogenic?

ABCB4 p.Arg469fs (c.14061409del) is classified Likely pathogenic in ABCB4 (ClinVar, Single submitter, 1 submitter). Absent from gnomAD; Associated with ABCB4-related disorder.

What condition is associated with ABCB4 p.Arg469fs (c.1406_1409del)?

ABCB4 p.Arg469fs (c.1406_1409del) is associated with ABCB4-related disorder (ClinVar).

How common is ABCB4 p.Arg469fs (c.1406_1409del) in the general population?

ABCB4 p.Arg469fs (c.1406_1409del) is absent from gnomAD (gnomAD).

ABCB4 p.Arg469fs

c.1406_1409del · rs2546830021 · VCV2584520

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 13 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.2	GERP 0.68, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: ABCB4
Protein: p.Arg469fs
Coding: c.1406_1409del
MANE Select: NM_000443
dbSNP: rs2546830021
Type: Deletion
Location: chr7:87440350 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 469: an α-helix; the abc transporter 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.Val336fs Likely pathogenic ★ same condition
ABCB4 p.Arg469Lys Uncertain significance ★ ⚠ same residue
ABCB4 p.Arg469Trp Uncertain significance ★ ⚠ same residue
CROT p.Met469Thr 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

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-arg469fs (accessed [today's date]).

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