Is ABCB11 p.Cys475fs (c.1422del) pathogenic?

ABCB11 p.Cys475fs (c.1422del) is classified Pathogenic in ABCB11 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-05). Absent from gnomAD.

How common is ABCB11 p.Cys475fs (c.1422del) in the general population?

ABCB11 p.Cys475fs (c.1422del) is absent from gnomAD (gnomAD).

ABCB11 p.Cys475fs

c.1422del · rs2105967878 · VCV1451709

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; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.7	GERP -2.7, phastCons 0.92

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: ABCB11
Protein: p.Cys475fs
Coding: c.1422del
MANE Select: NM_003742
dbSNP: rs2105967878
Type: Deletion
Location: chr2:168973727 (GRCh38)
Gene constraint: LOEUF 0.739 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.23 · 9 PDB
Residue 475: a β-strand; the abc transporter 1 domain

Full ABCB11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCB11 p.Cys475Ter Pathogenic ★ same residue
ABCB11 c.3213+1del Pathogenic ★★ same type
ABCB11 p.Ala452fs Pathogenic ★★ same type
ABCB11 p.Arg830fs Pathogenic ★★ same type
ABCB11 p.Asn199fs Pathogenic/Likely pathogenic ★★ same type
ABCB11 p.Asp848fs Pathogenic/Likely pathogenic ★★ same type
ABCB11 p.Gln1058fs Pathogenic ★★ same type
ABCB11 p.Gly1267fs 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/abcb11-p-cys475fs (accessed [today's date]).

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