Is BEX2 p.Arg59Gly (c.175A>G) pathogenic?

BEX2 p.Arg59Gly (c.175A>G) is classified Uncertain significance in BEX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-03). AlphaMissense: ambiguous (0.5053); Ultra-rare (popmax 0.0229%, mid).

How common is BEX2 p.Arg59Gly (c.175A>G) in the general population?

BEX2 p.Arg59Gly (c.175A>G) is ultra-rare (popmax 0.0229%, mid) (gnomAD).

What do computational predictors say about BEX2 p.Arg59Gly (c.175A>G)?

AlphaMissense predicts ambiguous (score 0.5053) — an in-silico prediction, not a clinical call.

BEX2 p.Arg59Gly

c.175A>G · rs757494935 · VCV3133756

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5053 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0229%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5053	ambiguous
REVEL	0.174	moderately benign-leaning
SaProt	LLR -2.28	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.019	GERP 0.62, phastCons 0.006
Regional constraint	o/e 0.94	unconstrained · MANE · 383 bp · p 0.55 · regional, not allelic
Overall
CADD	22.0	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 0.0229% Middle Eastern · 1/4,373 alleles

Filtering AF 0.00573% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00521%

Overall 0.00562% 68/1,210,376 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0229%	4,373
European (non-Finnish)	0.00715%	13,990
South Asian	0.00352%	28,421
Remaining individualsnot grpmax-eligible	0.0021%	47,603

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.Arg59Gly
Coding: c.175A>G
MANE Select: NM_032621
dbSNP: rs757494935
Type: single nucleotide variant
Location: chrX:103309802 (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-arg59gly (accessed [today's date]).

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