Is ABCB6 p.Gln217Arg (c.650A>G) pathogenic?

ABCB6 p.Gln217Arg (c.650A>G) is classified Uncertain significance in ABCB6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-03). AlphaMissense: likely benign (0.0619); Very rare (popmax 0.00134%, afr); Associated with ABCB6-related disorder.

What condition is associated with ABCB6 p.Gln217Arg (c.650A>G)?

ABCB6 p.Gln217Arg (c.650A>G) is associated with ABCB6-related disorder (ClinVar).

How common is ABCB6 p.Gln217Arg (c.650A>G) in the general population?

ABCB6 p.Gln217Arg (c.650A>G) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about ABCB6 p.Gln217Arg (c.650A>G)?

AlphaMissense predicts likely benign (score 0.0619) — an in-silico prediction, not a clinical call.

ABCB6 p.Gln217Arg

c.650A>G · rs773484755 · VCV2629234

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0619 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABCB6-related disorder

Computational evidence

Protein change
AlphaMissense	0.0619	likely benign
REVEL	0.175	moderately benign-leaning
SaProt	LLR -6.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.7	GERP -4.4
Regional constraint	o/e 0.96	unconstrained · MANE · 8,732 bp · p 0.15 · regional, not allelic
Overall
CADD	6.869	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,726 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,613,046 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,726
European (non-Finnish)	0.000424%	235,951

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.Gln217Arg
Coding: c.650A>G
MANE Select: NM_005689
dbSNP: rs773484755
Type: single nucleotide variant
Location: chr2:219217707 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.17 · 16 PDB
Residue 217: the 'required for atpase activity' region

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

Disease context

ABCB6-related disorder

Similar variants

ABCB6 p.Gln217Lys Likely benign ★ ⚠ same residue
ABCB6 p.Asp799Asn Uncertain significance ★★ ⚠ same condition
ABCB6 p.Arg584His Uncertain significance ★ ⚠ same condition
ABCB6 p.Leu540Arg Uncertain significance ★ ⚠ same condition
ABCB6 p.Lys771Asn Uncertain significance ★ ⚠ same condition
ABCB6 p.Tyr530fs Likely pathogenic same condition
ABCB6 p.Ala164Thr Uncertain significance ★★ ⚠ same type
ABCB6 p.Ala57Thr Uncertain significance ★★ ⚠ 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/abcb6-p-gln217arg (accessed [today's date]).

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