Is BEND5 p.Glu230Val (c.689A>T) pathogenic?

BEND5 p.Glu230Val (c.689A>T) is classified Uncertain significance in BEND5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-09). AlphaMissense: likely pathogenic (0.8112); Ultra-rare (popmax 0.0226%, amr).

How common is BEND5 p.Glu230Val (c.689A>T) in the general population?

BEND5 p.Glu230Val (c.689A>T) is ultra-rare (popmax 0.0226%, amr) (gnomAD).

What do computational predictors say about BEND5 p.Glu230Val (c.689A>T)?

AlphaMissense predicts likely pathogenic (score 0.8112) — an in-silico prediction, not a clinical call.

BEND5 p.Glu230Val

c.689A>T · rs747657670 · VCV3133711

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8112 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0226%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8112	likely pathogenic
REVEL	0.348	indeterminate
SaProt	LLR -8.44	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 19 kb · p 0.01 · regional, not allelic
Overall
CADD	29.4	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 0.0226% Admixed American · 13/57,592 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00244% 39/1,600,354 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0226%	4,430
Remaining individualsnot grpmax-eligible	0.00971%	10,296
European (non-Finnish)	0.0017%	58,706

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.Glu230Val
Coding: c.689A>T
MANE Select: NM_032785 · reported on NM_024603
dbSNP: rs747657670
Type: single nucleotide variant
Location: chr1:48758956 (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-glu230val (accessed [today's date]).

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