Is ABCB4 p.Gln520Ter (c.1558C>T) pathogenic?

ABCB4 p.Gln520Ter (c.1558C>T) is classified Pathogenic in ABCB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-19). Very rare (popmax 8.48e-05%, nfe).

How common is ABCB4 p.Gln520Ter (c.1558C>T) in the general population?

ABCB4 p.Gln520Ter (c.1558C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

ABCB4 p.Gln520Ter

c.1558C>T · VCV4713392

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 13 of 28
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP 0.067, phastCons 0.99
Overall
CADD	38.0	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 8.48e-05% European (non-Finnish) · 1/1,179,374 alleles

Overall 0.000657% 1/152,216 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.Gln520Ter
Coding: c.1558C>T
MANE Select: NM_000443
Type: single nucleotide variant
Location: chr7:87440201 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 520: a β-strand; the abc transporter 1 domain

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

Similar variants

ABCB4 c.1006-2A>C Pathogenic ★★ same type
ABCB4 c.1356+2T>C Pathogenic/Likely pathogenic ★★ same type
ABCB4 c.1560+1G>A Likely pathogenic ★★ same type
ABCB4 c.2064+3A>T Likely pathogenic ★★ same type
ABCB4 c.2211+1G>A Pathogenic/Likely pathogenic ★★ same type
ABCB4 c.2682+1G>A Pathogenic/Likely pathogenic ★★ same type
ABCB4 c.2783+1G>T Pathogenic/Likely pathogenic ★★ same type
ABCB4 c.286+1G>A 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-gln520ter (accessed [today's date]).

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