Is ABCB4 p.Asp564fs (c.1690_1702del) pathogenic?

ABCB4 p.Asp564fs (c.16901702del) is classified Pathogenic in ABCB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). Very rare (popmax 8.47e-05%, nfe).

How common is ABCB4 p.Asp564fs (c.1690_1702del) in the general population?

ABCB4 p.Asp564fs (c.1690_1702del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

ABCB4 p.Asp564fs

c.1690_1702del · rs1250100253 · VCV2777505

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 14 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,014 alleles

Overall 0.000657% 1/152,158 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.Asp564fs
Coding: c.1690_1702del
MANE Select: NM_000443
dbSNP: rs1250100253
Type: Deletion
Location: chr7:87439696 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 564: the abc transporter 1 domain; a UniProt-annotated variant site (in pfic3)

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

Similar variants

ABCB4 p.Asp564Ala Uncertain significance ★ ⚠ same residue
ABCB4 p.Asp564Gly Uncertain significance ★ ⚠ same residue
ABCB4 p.Asp564= Likely benign ★ same residue
ABCB4 p.Asp682fs Pathogenic ★★ same type
ABCB4 p.Gln458fs Pathogenic ★★ same type
ABCB4 p.Leu518fs Pathogenic/Likely pathogenic ★★ same type
ABCB4 p.Lys1026fs Pathogenic/Likely pathogenic ★★ same type
ABCB4 p.Lys30fs Pathogenic/Likely pathogenic ★★ same type

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-asp564fs (accessed [today's date]).

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