Is ABCB6 p.Phe27Cys (c.80T>G) pathogenic?

ABCB6 p.Phe27Cys (c.80T>G) is classified Conflicting classifications of pathogenicity in ABCB6 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-06-10). AlphaMissense: ambiguous (0.409); Ultra-rare (popmax 0.0661%, mid); Associated with Inborn genetic diseases.

What condition is associated with ABCB6 p.Phe27Cys (c.80T>G)?

ABCB6 p.Phe27Cys (c.80T>G) is associated with Inborn genetic diseases (ClinVar).

How common is ABCB6 p.Phe27Cys (c.80T>G) in the general population?

ABCB6 p.Phe27Cys (c.80T>G) is ultra-rare (popmax 0.0661%, mid) (gnomAD).

What do computational predictors say about ABCB6 p.Phe27Cys (c.80T>G)?

AlphaMissense predicts ambiguous (score 0.409) — an in-silico prediction, not a clinical call.

ABCB6 p.Phe27Cys

c.80T>G · rs763255664 · VCV2173907

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.409 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0661%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.409	ambiguous
REVEL	0.384	indeterminate
SaProt	LLR -6.47	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 1.2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 8,732 bp · p 0.15 · regional, not allelic
Overall
CADD	21.2	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 0.0661% Middle Eastern · 4/6,050 alleles

Filtering AF 0.0241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0198%

Overall 0.0131% 211/1,612,512 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0661%	1,513
East Asian	0.0379%	2,639
Admixed American	0.035%	2,857
Ashkenazi Jewishnot grpmax-eligible	0.0304%	3,287
Finnishnot grpmax-eligible	0.0302%	3,311
African / African-American	0.0253%	3,950
Remaining individualsnot grpmax-eligible	0.0192%	5,205
European (non-Finnish)	0.00882%	11,343
South Asian	0.00659%	15,173

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.Phe27Cys
Coding: c.80T>G
MANE Select: NM_005689
dbSNP: rs763255664
Type: single nucleotide variant
Location: chr2:219218594 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.17 · 16 PDB
Residue 27: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCB6 p.Phe27= Likely benign ★ same residue
ABCB6 p.Ala57Thr Uncertain significance ★★ ⚠ same condition
ABCB6 p.Ala66Thr Uncertain significance ★★ ⚠ same condition
ABCB6 p.Arg439Cys Uncertain significance ★★ ⚠ same condition
ABCB6 p.Arg450Gln Uncertain significance ★★ ⚠ same condition
ABCB6 p.Arg685His Uncertain significance ★★ ⚠ same condition
ABCB6 p.Arg688Gly Uncertain significance ★★ ⚠ same condition
ABCB6 p.Arg688His 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-phe27cys (accessed [today's date]).

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