Is BEND2 p.Ser531Cys (c.1591A>T) pathogenic?

BEND2 p.Ser531Cys (c.1591A>T) is classified Uncertain significance in BEND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-05). AlphaMissense: likely benign (0.0761); Ultra-rare (popmax 0.089%, eas).

How common is BEND2 p.Ser531Cys (c.1591A>T) in the general population?

BEND2 p.Ser531Cys (c.1591A>T) is ultra-rare (popmax 0.089%, eas) (gnomAD).

What do computational predictors say about BEND2 p.Ser531Cys (c.1591A>T)?

AlphaMissense predicts likely benign (score 0.0761) — an in-silico prediction, not a clinical call.

BEND2 p.Ser531Cys

c.1591A>T · rs761591084 · VCV2609898

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0761 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.089%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0761	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -7.49	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 -0.28	GERP -2.9
Regional constraint	o/e 1.00	unconstrained · MANE · 50 kb · p 0.98 · regional, not allelic
Overall
CADD	0.754	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 0.089% East Asian · 30/33,716 alleles

Filtering AF 0.064% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0556%

Overall 0.00256% 31/1,209,508 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.089%	1,124
Remaining individualsnot grpmax-eligible	0.0021%	47,615

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.Ser531Cys
Coding: c.1591A>T
MANE Select: NM_153346
dbSNP: rs761591084
Type: single nucleotide variant
Location: chrX:18177608 (GRCh38)
Structure: AlphaFold pLDDT 49.94
Residue 531: 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-ser531cys (accessed [today's date]).

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