Is ABCB6 p.Arg477Gln (c.1430G>A) pathogenic?

ABCB6 p.Arg477Gln (c.1430G>A) is classified Uncertain significance in ABCB6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-12). AlphaMissense: likely benign (0.0724); Very rare (popmax 0.00329%, sas); Associated with Inborn genetic diseases.

What condition is associated with ABCB6 p.Arg477Gln (c.1430G>A)?

ABCB6 p.Arg477Gln (c.1430G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ABCB6 p.Arg477Gln (c.1430G>A) in the general population?

ABCB6 p.Arg477Gln (c.1430G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about ABCB6 p.Arg477Gln (c.1430G>A)?

AlphaMissense predicts likely benign (score 0.0724) — an in-silico prediction, not a clinical call.

ABCB6 p.Arg477Gln

c.1430G>A · rs749179479 · VCV2285556

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0724 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0724	likely benign
REVEL	0.308	indeterminate
SaProt	LLR -7.16	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 -1.5	GERP -3.8
Regional constraint	o/e 0.96	unconstrained · MANE · 8,732 bp · p 0.15 · regional, not allelic
Overall
CADD	12.41	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 0.00329% South Asian · 3/91,086 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00167% 27/1,614,072 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,362
Remaining individualsnot grpmax-eligible	0.0032%	31,244
East Asian	0.00223%	44,898
European (non-Finnish)	0.00169%	59,003
Finnishnot grpmax-eligible	0.00156%	64,014

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.Arg477Gln
Coding: c.1430G>A
MANE Select: NM_005689
dbSNP: rs749179479
Type: single nucleotide variant
Location: chr2:219214143 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.17 · 16 PDB
Residue 477: the abc transmembrane type-1 domain; an α-helix

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.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
ABCB6 p.Asn545Ser 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-arg477gln (accessed [today's date]).

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