Is BEND5 p.Glu45Lys (c.133G>A) pathogenic?

BEND5 p.Glu45Lys (c.133G>A) is classified Uncertain significance in BEND5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-28). AlphaMissense: likely benign (0.2019); Ultra-rare (popmax 0.0326%, eas).

How common is BEND5 p.Glu45Lys (c.133G>A) in the general population?

BEND5 p.Glu45Lys (c.133G>A) is ultra-rare (popmax 0.0326%, eas) (gnomAD).

What do computational predictors say about BEND5 p.Glu45Lys (c.133G>A)?

AlphaMissense predicts likely benign (score 0.2019) — an in-silico prediction, not a clinical call.

BEND5 p.Glu45Lys

c.133G>A · VCV3260791

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2019 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0326%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2019	likely benign
REVEL	0.317	indeterminate
SaProt	LLR -8.11	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.5	GERP 1.9, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 200 bp · p 0.41 · regional, not allelic
Overall
CADD	24.3	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 0.0326% East Asian · 12/36,784 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00362% 55/1,518,540 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0326%	3,065
Remaining individualsnot grpmax-eligible	0.00852%	11,744
South Asian	0.00744%	13,449
European (non-Finnish)	0.00282%	35,444

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: BEND5
Protein: p.Glu45Lys
Coding: c.133G>A
MANE Select: NM_032785 · reported on NM_024603
Type: single nucleotide variant
Location: chr1:48776699 (GRCh38)

Full BEND5 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/bend5-p-glu45lys (accessed [today's date]).

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