Is ZBED4 p.Lys891Arg (c.2672A>G) pathogenic?

ZBED4 p.Lys891Arg (c.2672A>G) is classified Likely benign in ZBED4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-24). AlphaMissense: likely benign (0.0589); Ultra-rare (popmax 0.0476%, sas).

How common is ZBED4 p.Lys891Arg (c.2672A>G) in the general population?

ZBED4 p.Lys891Arg (c.2672A>G) is ultra-rare (popmax 0.0476%, sas) (gnomAD).

What do computational predictors say about ZBED4 p.Lys891Arg (c.2672A>G)?

AlphaMissense predicts likely benign (score 0.0589) — an in-silico prediction, not a clinical call.

ZBED4 p.Lys891Arg

c.2672A>G · VCV3818187

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0589 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0476%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0589	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -3.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.6	GERP -3.3
Regional constraint	o/e 0.76	unconstrained · MANE · 913 bp · p 1.1e-06 · regional, not allelic
Overall
CADD	0.014	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 0.0476% South Asian · 43/90,396 alleles

Filtering AF 0.0362% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0323%

Overall 0.00319% 51/1,600,890 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0476%	2,102
Remaining individualsnot grpmax-eligible	0.0097%	10,309
Admixed American	0.00169%	59,300
European (non-Finnish)	8.55e-05%	1,170,187

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: ZBED4
Protein: p.Lys891Arg
Coding: c.2672A>G
MANE Select: NM_024105 · reported on NM_014838
Type: single nucleotide variant
Location: chr22:49886334 (GRCh38)

Full ZBED4 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/zbed4-p-lys891arg (accessed [today's date]).

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