Is BEND2 p.Arg511Cys (c.1531C>T) pathogenic?

BEND2 p.Arg511Cys (c.1531C>T) is classified Uncertain significance in BEND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.1195); Ultra-rare (popmax 0.0457%, mid).

How common is BEND2 p.Arg511Cys (c.1531C>T) in the general population?

BEND2 p.Arg511Cys (c.1531C>T) is ultra-rare (popmax 0.0457%, mid) (gnomAD).

What do computational predictors say about BEND2 p.Arg511Cys (c.1531C>T)?

AlphaMissense predicts likely benign (score 0.1195) — an in-silico prediction, not a clinical call.

BEND2 p.Arg511Cys

c.1531C>T · rs753955004 · VCV2385409

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1195 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0457%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1195	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -9.28	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.28	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 0.78	GERP -2.9, phastCons 0.062
Regional constraint	o/e 1.00	unconstrained · MANE · 50 kb · p 0.98 · regional, not allelic
Overall
CADD	17.35	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 0.0457% Middle Eastern · 2/4,373 alleles

Filtering AF 0.00948% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00726%

Overall 0.00497% 60/1,208,339 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0457%	2,186
South Asian	0.0176%	5,673
Remaining individualsnot grpmax-eligible	0.0105%	9,516
European (non-Finnish)	0.00447%	22,352
East Asian	0.00297%	33,705
Finnishnot grpmax-eligible	0.00215%	46,476
African / African-American	0.00175%	57,037

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: BEND2
Protein: p.Arg511Cys
Coding: c.1531C>T
MANE Select: NM_153346
dbSNP: rs753955004
Type: single nucleotide variant
Location: chrX:18177668 (GRCh38)
Structure: AlphaFold pLDDT 49.94
Residue 511: the ben 1 domain

Full BEND2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BEND2 p.Gln198His Benign ★★ same type
BEND2 p.Gly580Val Benign ★★ same type
BEND2 p.Ser183Ile Benign ★★ ⚠ same type
BEND2 p.Thr367= Likely benign ★★ same type
BEND2 p.Val261Gly Benign ★★ same type
BEND2 p.Ala185Gly Uncertain significance ★ ⚠ same type
BEND2 p.Ala193Thr Uncertain significance ★ ⚠ same type
BEND2 p.Ala222Ser 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/bend2-p-arg511cys (accessed [today's date]).

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