Is BEX3 p.Leu87= (c.261C>T) pathogenic?

BEX3 p.Leu87= (c.261C>T) is classified Likely benign in BEX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-01). Ultra-rare (popmax 0.0333%, nfe).

How common is BEX3 p.Leu87= (c.261C>T) in the general population?

BEX3 p.Leu87= (c.261C>T) is ultra-rare (popmax 0.0333%, nfe) (gnomAD).

BEX3 p.Leu87=

c.261C>T · rs147893779 · VCV2661095

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0333%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.71	GERP 3.4
Overall
CADD	8.756	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0333% European (non-Finnish) · 298/893,783 alleles

Filtering AF 0.0302% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0289%

Overall 0.0253% 305/1,207,449 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0333%	2,999
Remaining individualsnot grpmax-eligible	0.00842%	11,877
Admixed American	0.00219%	45,696
Finnishnot grpmax-eligible	0.00215%	46,554
African / African-American	0.00175%	57,042

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: BEX3
Protein: p.Leu87=
Coding: c.261C>T
MANE Select: NM_206917
dbSNP: rs147893779
Type: single nucleotide variant
Location: chrX:103377782 (GRCh38)
Structure: AlphaFold pLDDT 65.81
Residue 87: the 'interaction with 14-3-3 epsilon' region; the 'interaction with p75ntr/ngfr' region

Full BEX3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/bex3-p-leu87 (accessed [today's date]).

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