Is BEND3 p.Lys239Arg (c.716A>G) pathogenic?

BEND3 p.Lys239Arg (c.716A>G) is classified Uncertain significance in BEND3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-17). AlphaMissense: likely benign (0.092); Ultra-rare (popmax 0.0165%, sas).

How common is BEND3 p.Lys239Arg (c.716A>G) in the general population?

BEND3 p.Lys239Arg (c.716A>G) is ultra-rare (popmax 0.0165%, sas) (gnomAD).

What do computational predictors say about BEND3 p.Lys239Arg (c.716A>G)?

AlphaMissense predicts likely benign (score 0.092) — an in-silico prediction, not a clinical call.

BEND3 p.Lys239Arg

c.716A>G · rs782067709 · VCV3133692

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.092 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.092	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -3.04	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 2.4	GERP 0.82, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 30 kb · p 3.2e-09 · regional, not allelic
Overall
CADD	20.6	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 0.0165% South Asian · 15/91,072 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.00103% 15/1,461,846 alleles · ultra-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: BEND3
Protein: p.Lys239Arg
Coding: c.716A>G
MANE Select: NM_001367314
dbSNP: rs782067709
Type: single nucleotide variant
Location: chr6:107070475 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.11 · 2 PDB

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

Similar variants

BEND3 p.Lys239Ile Uncertain significance ★ ⚠ same residue
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

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-lys239arg (accessed [today's date]).

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