Is ZBED2 p.Glu171Asp (c.513G>C) pathogenic?

ZBED2 p.Glu171Asp (c.513G>C) is classified Uncertain significance in ZBED2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-15). AlphaMissense: likely pathogenic (0.6189); Very rare (popmax 0.000932%, nfe).

How common is ZBED2 p.Glu171Asp (c.513G>C) in the general population?

ZBED2 p.Glu171Asp (c.513G>C) is very rare (popmax 0.000932%, nfe) (gnomAD).

What do computational predictors say about ZBED2 p.Glu171Asp (c.513G>C)?

AlphaMissense predicts likely pathogenic (score 0.6189) — an in-silico prediction, not a clinical call.

ZBED2 p.Glu171Asp

c.513G>C · rs776869952 · VCV2605195

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6189 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6189	likely pathogenic
REVEL	0.104	moderately benign-leaning
SaProt	LLR -11.52	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.2	GERP 1.4, phastCons 0.42
Regional constraint	o/e 1.01	unconstrained · MANE · 653 bp · p 0.81 · regional, not allelic
Overall
CADD	22.9	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 0.000932% European (non-Finnish) · 11/1,179,696 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000753% 11/1,461,276 alleles · very rare

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.Glu171Asp
Coding: c.513G>C
MANE Select: NM_005816 · reported on NM_024508
dbSNP: rs776869952
Type: single nucleotide variant
Location: chr3:111593689 (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-glu171asp (accessed [today's date]).

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