Is BEND3 p.Phe284Ile (c.850T>A) pathogenic?

BEND3 p.Phe284Ile (c.850T>A) is classified Uncertain significance in BEND3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely benign (0.1071); Absent from gnomAD v4.1.

How common is BEND3 p.Phe284Ile (c.850T>A) in the general population?

BEND3 p.Phe284Ile (c.850T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BEND3 p.Phe284Ile (c.850T>A)?

AlphaMissense predicts likely benign (score 0.1071) — an in-silico prediction, not a clinical call.

BEND3 p.Phe284Ile

c.850T>A · VCV4645744

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1071 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1071	likely benign
REVEL	0.152	moderately benign-leaning
SaProt	LLR -6.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP -0.37, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 30 kb · p 3.2e-09 · regional, not allelic
Overall
CADD	21.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BEND3
Protein: p.Phe284Ile
Coding: c.850T>A
MANE Select: NM_001367314
Type: single nucleotide variant
Location: chr6:107070341 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.11 · 2 PDB
Residue 284: the ben 1 domain

Full BEND3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BEND3 p.Ala102Val Uncertain significance ★ ⚠ same type
BEND3 p.Ala122Gly Uncertain significance ★ ⚠ same type
BEND3 p.Ala161Thr Uncertain significance ★ ⚠ same type
BEND3 p.Ala250Val Uncertain significance ★ ⚠ same type
BEND3 p.Ala251Thr Uncertain significance ★ ⚠ same type
BEND3 p.Ala28Asp Uncertain significance ★ ⚠ same type
BEND3 p.Ala355Thr Uncertain significance ★ ⚠ same type
BEND3 p.Ala387Thr Uncertain significance ★ ⚠ same type

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/bend3-p-phe284ile (accessed [today's date]).

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