Is ABCB6 p.Trp154fs (c.459del) pathogenic?

ABCB6 p.Trp154fs (c.459del) is classified Uncertain significance in ABCB6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-18). Rare (popmax 0.149%, eas); Associated with dyschromatosis universalis hereditaria 3.

What condition is associated with ABCB6 p.Trp154fs (c.459del)?

ABCB6 p.Trp154fs (c.459del) is associated with dyschromatosis universalis hereditaria 3 (ClinVar).

How common is ABCB6 p.Trp154fs (c.459del) in the general population?

ABCB6 p.Trp154fs (c.459del) is rare (popmax 0.149%, eas) (gnomAD).

How is Dyschromatosis universalis hereditaria inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ABCB6 p.Trp154fs

c.459del · rs755723161 · VCV1686417

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.149%, eas)

Conditions

dyschromatosis universalis hereditaria 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Overall
CADD	27.1	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 0.149% East Asian · 67/44,890 alleles

Filtering AF 0.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.11%

Overall 0.00421% 68/1,613,846 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.149%	670
South Asian	0.0011%	91,088

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: ABCB6
Protein: p.Trp154fs
Coding: c.459del
MANE Select: NM_005689
dbSNP: rs755723161
Type: Deletion
Location: chr2:219218215 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.17 · 16 PDB
Residue 154: the 'required for atpase activity' region; the 'required for the lysosomal targeting' region

Full ABCB6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dyschromatosis universalis hereditaria 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Dyschromatosis universalis hereditaria (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood, Infancy

Similar variants

ABCB6 p.Glu220Val Uncertain significance ★★ ⚠ same condition
ABCB6 p.Phe565Ser Uncertain significance ★★ ⚠ same condition
ABCB6 c.688-9C>T Benign/Likely benign ★★ same condition
ABCB6 c.1452+2T>A Likely pathogenic ★ same condition
ABCB6 c.1864-4A>G Uncertain significance ★ same condition
ABCB6 p.Arg375Trp Conflicting classifications of pathogenicity ★ same condition
ABCB6 p.Asn677Tyr Uncertain significance ★ ⚠ same condition
ABCB6 p.Thr787Ala Uncertain significance ★ ⚠ 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/abcb6-p-trp154fs (accessed [today's date]).

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