Is ZBED2 p.Arg4Gln (c.11G>A) pathogenic?

ZBED2 p.Arg4Gln (c.11G>A) is classified Uncertain significance in ZBED2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely benign (0.085); Ultra-rare (popmax 0.0321%, afr).

How common is ZBED2 p.Arg4Gln (c.11G>A) in the general population?

ZBED2 p.Arg4Gln (c.11G>A) is ultra-rare (popmax 0.0321%, afr) (gnomAD).

What do computational predictors say about ZBED2 p.Arg4Gln (c.11G>A)?

AlphaMissense predicts likely benign (score 0.085) — an in-silico prediction, not a clinical call.

ZBED2 p.Arg4Gln

c.11G>A · VCV4606369

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.085 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0321%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.085	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -7.15	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.1	GERP -0.84
Regional constraint	o/e 1.01	unconstrained · MANE · 653 bp · p 0.81 · regional, not allelic
Overall
CADD	14.75	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 0.0321% African / African-American · 24/74,708 alleles

Filtering AF 0.0221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0188%

Overall 0.00232% 37/1,593,538 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0321%	3,113
Middle Eastern	0.0168%	5,952
Admixed American	0.0017%	58,706
European (non-Finnish)	0.000941%	106,261

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: ZBED2
Protein: p.Arg4Gln
Coding: c.11G>A
MANE Select: NM_005816 · reported on NM_024508
Type: single nucleotide variant
Location: chr3:111594191 (GRCh38)

Full ZBED2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/zbed2-p-arg4gln (accessed [today's date]).

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