Is BEX2 p.Arg57Cys (c.169C>T) pathogenic?

BEX2 p.Arg57Cys (c.169C>T) is classified Uncertain significance in BEX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). AlphaMissense: likely benign (0.1993); Ultra-rare (popmax 0.0345%, nfe).

How common is BEX2 p.Arg57Cys (c.169C>T) in the general population?

BEX2 p.Arg57Cys (c.169C>T) is ultra-rare (popmax 0.0345%, nfe) (gnomAD).

What do computational predictors say about BEX2 p.Arg57Cys (c.169C>T)?

AlphaMissense predicts likely benign (score 0.1993) — an in-silico prediction, not a clinical call.

BEX2 p.Arg57Cys

c.169C>T · rs199515438 · VCV3133755

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1993 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0345%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1993	likely benign
REVEL	0.144	moderately benign-leaning
SaProt	LLR -8.47	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 0.15	GERP -2
Regional constraint	o/e 0.94	unconstrained · MANE · 383 bp · p 0.55 · regional, not allelic
Overall
CADD	21.6	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 0.0345% European (non-Finnish) · 309/895,305 alleles

Filtering AF 0.0313% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0301%

Overall 0.0277% 335/1,210,205 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0345%	2,897
Ashkenazi Jewishnot grpmax-eligible	0.0182%	5,509
Remaining individualsnot grpmax-eligible	0.0168%	5,950
Admixed American	0.0153%	6,545
Finnishnot grpmax-eligible	0.00643%	15,543
African / African-American	0.00525%	19,055
South Asian	0.00176%	56,847

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: BEX2
Protein: p.Arg57Cys
Coding: c.169C>T
MANE Select: NM_032621
dbSNP: rs199515438
Type: single nucleotide variant
Location: chrX:103309808 (GRCh38)
Structure: AlphaFold pLDDT 68.93

Full BEX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BEX2 p.Asn32Asp Benign ★★ same type
BEX2 c.-12G>A Uncertain significance ★ same type
BEX2 c.-48C>G Uncertain significance ★ same type
BEX2 c.-60G>A Uncertain significance ★ same type
BEX2 c.-62G>A Uncertain significance ★ same type
BEX2 c.-72G>A Uncertain significance ★ same type
BEX2 c.-75G>A Uncertain significance ★ same type
BEX2 c.-75G>C 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/bex2-p-arg57cys (accessed [today's date]).

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