Is ABCB6 p.Ser170Gly (c.508A>G) pathogenic?

ABCB6 p.Ser170Gly (c.508A>G) is classified Pathogenic in ABCB6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2013-09-01). AlphaMissense: likely benign (0.245); Absent from gnomAD v4.1; Associated with dyschromatosis universalis hereditaria 3.

What condition is associated with ABCB6 p.Ser170Gly (c.508A>G)?

ABCB6 p.Ser170Gly (c.508A>G) is associated with dyschromatosis universalis hereditaria 3 (ClinVar).

How common is ABCB6 p.Ser170Gly (c.508A>G) in the general population?

ABCB6 p.Ser170Gly (c.508A>G) is absent from gnomAD v4.1 (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.Ser170Gly (c.508A>G)?

AlphaMissense predicts likely benign (score 0.245) — an in-silico prediction, not a clinical call.

ABCB6 p.Ser170Gly

c.508A>G · rs397514757 · VCV64647

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.245 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

dyschromatosis universalis hereditaria 3

Computational evidence

Protein change
AlphaMissense	0.245	likely benign ⚠ discordant with ClinVar
REVEL	0.461	indeterminate
SaProt	LLR -4.16	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.4, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 8,732 bp · p 0.15 · regional, not allelic
Overall
CADD	23.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCB6
Protein: p.Ser170Gly
Coding: c.508A>G
MANE Select: NM_005689
dbSNP: rs397514757
Type: single nucleotide variant
Location: chr2:219218166 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.17 · 16 PDB
Residue 170: the 'required for atpase activity' region; the 'required for the lysosomal targeting' region; a UniProt-annotated variant site (in duh3; the protein is retained in the golgi apparatus)

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-ser170gly (accessed [today's date]).

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