Is BTBD9 p.Gln563Arg (c.1688A>G) pathogenic?

BTBD9 p.Gln563Arg (c.1688A>G) is classified Uncertain significance in BTBD9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-25). AlphaMissense: likely benign (0.0681); Very rare (popmax 0.00833%, amr).

How common is BTBD9 p.Gln563Arg (c.1688A>G) in the general population?

BTBD9 p.Gln563Arg (c.1688A>G) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about BTBD9 p.Gln563Arg (c.1688A>G)?

AlphaMissense predicts likely benign (score 0.0681) — an in-silico prediction, not a clinical call.

BTBD9 p.Gln563Arg

c.1688A>G · VCV3482831

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0681 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0681	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -6.01	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 1.2	GERP 0.98, phastCons 0.98
Regional constraint	o/e 0.78	unconstrained · MANE · 423 kb · p 2.8e-09 · regional, not allelic
Overall
CADD	17.08	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 0.00833% Admixed American · 5/60,008 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00124% 20/1,614,042 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,002
South Asian	0.00549%	18,215
Remaining individualsnot grpmax-eligible	0.0016%	62,476
European (non-Finnish)	0.000763%	131,110

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: BTBD9
Protein: p.Gln563Arg
Coding: c.1688A>G
MANE Select: NM_001099272
Type: single nucleotide variant
Location: chr6:38175136 (GRCh38)
Gene constraint: LOEUF 0.959 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.71
Residue 563: the 'disordered' region

Full BTBD9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BTBD9 p.Gln563Leu Uncertain significance ★ ⚠ same residue
BTBD9 p.Ala100Val Uncertain significance ★ ⚠ same type
BTBD9 p.Ala28Thr Uncertain significance ★ ⚠ same type
BTBD9 p.Ala476Thr Uncertain significance ★ ⚠ same type
BTBD9 p.Ala590Val Uncertain significance ★ ⚠ same type
BTBD9 p.Ala76Val Uncertain significance ★ ⚠ same type
BTBD9 p.Arg257Gly Uncertain significance ★ ⚠ same type
BTBD9 p.Arg319His 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/btbd9-p-gln563arg (accessed [today's date]).

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