Is BEND6 p.Trp179Arg (c.535T>C) pathogenic?

BEND6 p.Trp179Arg (c.535T>C) is classified Uncertain significance in BEND6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-28). AlphaMissense: likely pathogenic (0.9981); Very rare (popmax 0.00369%, amr).

How common is BEND6 p.Trp179Arg (c.535T>C) in the general population?

BEND6 p.Trp179Arg (c.535T>C) is very rare (popmax 0.00369%, amr) (gnomAD).

What do computational predictors say about BEND6 p.Trp179Arg (c.535T>C)?

AlphaMissense predicts likely pathogenic (score 0.9981) — an in-silico prediction, not a clinical call.

BEND6 p.Trp179Arg

c.535T>C · VCV4645765

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9981 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00369%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9981	likely pathogenic · top 3% in BEND6
REVEL	0.413	indeterminate
SaProt	LLR -9.71	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 37 kb · p 0.065 · regional, not allelic
Overall
CADD	29.2	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 0.00369% Admixed American · 2/54,186 alleles

Filtering AF 0.000612% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000264%

Overall 0.000774% 11/1,420,834 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00369%	27,093
European (non-Finnish)	0.000775%	129,026

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: BEND6
Protein: p.Trp179Arg
Coding: c.535T>C
MANE Select: NM_152731
Type: single nucleotide variant
Location: chr6:57017222 (GRCh38)
Gene constraint: LOEUF 1.085 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.39 · 2 PDB
Residue 179: the ben domain; an α-helix

Full BEND6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BEND6 p.Ala129Ser Uncertain significance ★ ⚠ same type
BEND6 p.Ala145Thr Uncertain significance ★ ⚠ same type
BEND6 p.Arg183Cys Uncertain significance ★ ⚠ same type
BEND6 p.Arg85Trp Uncertain significance ★ ⚠ same type
BEND6 p.Asn137Ser Uncertain significance ★ ⚠ same type
BEND6 p.Asn246Ser Uncertain significance ★ ⚠ same type
BEND6 p.Asn31Lys Uncertain significance ★ ⚠ same type
BEND6 p.Cys148Phe 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/bend6-p-trp179arg (accessed [today's date]).

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