Is ABCB9 p.Arg562Trp (c.1684C>T) pathogenic?

ABCB9 p.Arg562Trp (c.1684C>T) is classified Uncertain significance in ABCB9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-08). AlphaMissense: likely benign (0.1514); Very rare (popmax 0.00334%, amr).

How common is ABCB9 p.Arg562Trp (c.1684C>T) in the general population?

ABCB9 p.Arg562Trp (c.1684C>T) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about ABCB9 p.Arg562Trp (c.1684C>T)?

AlphaMissense predicts likely benign (score 0.1514) — an in-silico prediction, not a clinical call.

ABCB9 p.Arg562Trp

c.1684C>T · VCV3867690

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1514 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1514	likely benign
REVEL	0.555	indeterminate
SaProt	LLR -14.31	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 30 kb · p 0.00058 · regional, not allelic
Overall
CADD	25.1	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 0.00334% Admixed American · 2/59,900 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00229% 37/1,613,454 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,950
European (non-Finnish)	0.00271%	36,870
African / African-American	0.00267%	37,459
Remaining individualsnot grpmax-eligible	0.0016%	62,446

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: ABCB9
Protein: p.Arg562Trp
Coding: c.1684C>T
MANE Select: NM_019625
Type: single nucleotide variant
Location: chr12:122940170 (GRCh38)
Gene constraint: LOEUF 0.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.76
Residue 562: the abc transporter domain

Full ABCB9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCB9 p.Arg562Gln Uncertain significance ★ ⚠ same residue
ABCB9 p.Ala151Val Uncertain significance ★ ⚠ same type
ABCB9 p.Ala169Thr Uncertain significance ★ ⚠ same type
ABCB9 p.Ala364Val Uncertain significance ★ ⚠ same type
ABCB9 p.Ala368Val Uncertain significance ★ ⚠ same type
ABCB9 p.Ala447Thr Uncertain significance ★ ⚠ same type
ABCB9 p.Ala641Ser Uncertain significance ★ ⚠ same type
ABCB9 p.Ala641Thr 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/abcb9-p-arg562trp (accessed [today's date]).

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