Is ABCB6 p.Trp64Cys (c.192G>C) pathogenic?

ABCB6 p.Trp64Cys (c.192G>C) is classified Uncertain significance in ABCB6 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-25). AlphaMissense: ambiguous (0.387); Very rare (popmax 0.00441%, sas); Associated with dyschromatosis universalis hereditaria 3.

What condition is associated with ABCB6 p.Trp64Cys (c.192G>C)?

ABCB6 p.Trp64Cys (c.192G>C) is associated with dyschromatosis universalis hereditaria 3 (ClinVar).

How common is ABCB6 p.Trp64Cys (c.192G>C) in the general population?

ABCB6 p.Trp64Cys (c.192G>C) is very rare (popmax 0.00441%, sas) (gnomAD).

How is Dyschromatosis universalis hereditaria inherited?

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

What do computational predictors say about ABCB6 p.Trp64Cys (c.192G>C)?

AlphaMissense predicts ambiguous (score 0.387) — an in-silico prediction, not a clinical call.

ABCB6 p.Trp64Cys

c.192G>C · VCV3377363

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.387 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00441%, sas)

Conditions

dyschromatosis universalis hereditaria 3

Computational evidence

Protein change
AlphaMissense	0.387	ambiguous
REVEL	0.31	indeterminate
SaProt	LLR -5.85	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 1.1, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 8,732 bp · p 0.15 · regional, not allelic
Overall
CADD	20.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00441% South Asian · 4/90,766 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00109%

Overall 0.00192% 28/1,455,880 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00441%	22,691
European (non-Finnish)	0.00195%	51,212
Remaining individualsnot grpmax-eligible	0.00161%	62,216

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.Trp64Cys
Coding: c.192G>C
MANE Select: NM_005689
Type: single nucleotide variant
Location: chr2:219218482 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.17 · 16 PDB
Residue 64: 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-trp64cys (accessed [today's date]).

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