Is BEX4 p.Lys4Glu (c.10A>G) pathogenic?

BEX4 p.Lys4Glu (c.10A>G) is classified Uncertain significance in BEX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-10). AlphaMissense: likely benign (0.121); Ultra-rare (popmax 0.0121%, nfe).

How common is BEX4 p.Lys4Glu (c.10A>G) in the general population?

BEX4 p.Lys4Glu (c.10A>G) is ultra-rare (popmax 0.0121%, nfe) (gnomAD).

What do computational predictors say about BEX4 p.Lys4Glu (c.10A>G)?

AlphaMissense predicts likely benign (score 0.121) — an in-silico prediction, not a clinical call.

BEX4 p.Lys4Glu

c.10A>G · rs150891402 · VCV2406832

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.121 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.121	likely benign
REVEL	0.109	moderately benign-leaning
SaProt	LLR -4.59	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 4.7	GERP 1.9, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 359 bp · p 0.17 · regional, not allelic
Overall
CADD	21.8	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 0.0121% European (non-Finnish) · 105/866,466 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00954%

Overall 0.00996% 114/1,144,942 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0121%	8,252
Admixed American	0.0117%	8,551
South Asian	0.00649%	15,397
Remaining individualsnot grpmax-eligible	0.00447%	22,374

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: BEX4
Protein: p.Lys4Glu
Coding: c.10A>G
MANE Select: NM_001080425
dbSNP: rs150891402
Type: single nucleotide variant
Location: chrX:103216163 (GRCh38)
Structure: AlphaFold pLDDT 64.35
Residue 4: the 'disordered' region

Full BEX4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BEX4 p.Ala65Val Uncertain significance ★ ⚠ same type
BEX4 p.Arg104His Uncertain significance ★ ⚠ same type
BEX4 p.Arg104Ser Uncertain significance ★ ⚠ same type
BEX4 p.Arg52Trp Uncertain significance ★ ⚠ same type
BEX4 p.Arg54Gln Uncertain significance ★ ⚠ same type
BEX4 p.Arg63Gln Uncertain significance ★ ⚠ same type
BEX4 p.Asn112His Uncertain significance ★ ⚠ same type
BEX4 p.Asn11Ser 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/bex4-p-lys4glu (accessed [today's date]).

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