Is ABCB8 p.Gln532Arg (c.1595A>G) pathogenic?

ABCB8 p.Gln532Arg (c.1595A>G) is classified Uncertain significance in ABCB8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.0712); Ultra-rare (popmax 0.0165%, mid).

How common is ABCB8 p.Gln532Arg (c.1595A>G) in the general population?

ABCB8 p.Gln532Arg (c.1595A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about ABCB8 p.Gln532Arg (c.1595A>G)?

AlphaMissense predicts likely benign (score 0.0712) — an in-silico prediction, not a clinical call.

ABCB8 p.Gln532Arg

c.1595A>G · VCV4108231

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0712 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0712	likely benign
REVEL	0.325	indeterminate
SaProt	LLR -7.13	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 9.4	GERP 1.1, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 17 kb · p 0.036 · regional, not allelic
Overall
CADD	20.6	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM Q549R vs ClinVar Q532R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,046 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000344% 5/1,452,018 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,046
South Asian	0.0011%	91,036
European (non-Finnish)	0.000254%	393,096

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: ABCB8
Protein: p.Gln532Arg
Coding: c.1595A>G
MANE Select: NM_007188
Type: single nucleotide variant
Location: chr7:151041210 (GRCh38)
Gene constraint: LOEUF 0.894 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.01 · 2 PDB
Residue 532: the abc transporter domain; a β-strand

Full ABCB8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCB8 c.564+4C>T Benign ★★ same type
ABCB8 p.Ala101= Benign ★★ same type
ABCB8 p.Arg452Leu Benign ★★ ⚠ same type
ABCB8 p.His201= Benign ★★ same type
ABCB8 p.Leu124Val Benign ★★ same type
ABCB8 p.Ser39Asn Benign ★★ ⚠ same type
ABCB8 p.Val110= Benign ★★ same type
ABCB8 p.Val633= Benign ★★ 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/abcb8-p-gln532arg (accessed [today's date]).

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