Is BEND6 p.Arg85Trp (c.253C>T) pathogenic?

BEND6 p.Arg85Trp (c.253C>T) is classified Uncertain significance in BEND6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-04). AlphaMissense: likely benign (0.2432); Very rare (popmax 0.00549%, sas).

How common is BEND6 p.Arg85Trp (c.253C>T) in the general population?

BEND6 p.Arg85Trp (c.253C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about BEND6 p.Arg85Trp (c.253C>T)?

AlphaMissense predicts likely benign (score 0.2432) — an in-silico prediction, not a clinical call.

BEND6 p.Arg85Trp

c.253C>T · rs762196915 · VCV2269631

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2432 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2432	likely benign
REVEL	0.184	benign-leaning
SaProt	LLR -11.88	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.086	GERP -1.6
Regional constraint	o/e 0.90	unconstrained · MANE · 37 kb · p 0.065 · regional, not allelic
Overall
CADD	21.9	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 0.00549% South Asian · 5/91,030 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00254% 41/1,613,702 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,206
African / African-American	0.00534%	18,711
Remaining individualsnot grpmax-eligible	0.0032%	31,230
European (non-Finnish)	0.00254%	39,331

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.Arg85Trp
Coding: c.253C>T
MANE Select: NM_152731
dbSNP: rs762196915
Type: single nucleotide variant
Location: chr6:56992510 (GRCh38)
Gene constraint: LOEUF 1.085 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.39 · 2 PDB

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.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
BEND6 p.Cys71Arg 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-arg85trp (accessed [today's date]).

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