Is BEX4 p.Asn11Ser (c.32A>G) pathogenic?

BEX4 p.Asn11Ser (c.32A>G) is classified Uncertain significance in BEX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-28). AlphaMissense: likely benign (0.0835); Very rare (popmax 0.00553%, afr).

How common is BEX4 p.Asn11Ser (c.32A>G) in the general population?

BEX4 p.Asn11Ser (c.32A>G) is very rare (popmax 0.00553%, afr) (gnomAD).

What do computational predictors say about BEX4 p.Asn11Ser (c.32A>G)?

AlphaMissense predicts likely benign (score 0.0835) — an in-silico prediction, not a clinical call.

BEX4 p.Asn11Ser

c.32A>G · rs370714145 · VCV3133762

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0835 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00553%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0835	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -6.87	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 -0.62	GERP -0.55
Regional constraint	o/e 1.14	unconstrained · MANE · 359 bp · p 0.17 · regional, not allelic
Overall
CADD	3.973	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 0.00553% African / African-American · 3/54,291 alleles

Filtering AF 0.00224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00193%

Overall 0.00279% 32/1,147,321 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00553%	18,097
European (non-Finnish)	0.00323%	30,973
Finnishnot grpmax-eligible	0.00228%	43,805

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.Asn11Ser
Coding: c.32A>G
MANE Select: NM_001080425
dbSNP: rs370714145
Type: single nucleotide variant
Location: chrX:103216185 (GRCh38)
Structure: AlphaFold pLDDT 64.35
Residue 11: 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.Asn13Ser 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-asn11ser (accessed [today's date]).

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