Is ABCB4 p.Ala250fs (c.749del) pathogenic?

ABCB4 p.Ala250fs (c.749del) is classified Pathogenic in ABCB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-29). Absent from gnomAD.

How common is ABCB4 p.Ala250fs (c.749del) in the general population?

ABCB4 p.Ala250fs (c.749del) is absent from gnomAD (gnomAD).

ABCB4 p.Ala250fs

c.749del · rs2546854230 · VCV2713948

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 8 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.5	GERP -0.93

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.Ala250fs
Coding: c.749del
MANE Select: NM_000443
dbSNP: rs2546854230
Type: Deletion
Location: chr7:87450052 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 250: an α-helix; the abc transmembrane type-1 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.Ala250Thr Likely pathogenic ★ ⚠ same residue
ABCB4 p.Ala250Pro Uncertain significance ★ ⚠ same residue
ABCB4 p.Ala250Val Uncertain significance ★ ⚠ 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-ala250fs (accessed [today's date]).

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