Is BEX5 p.Arg88Ser (c.264G>C) pathogenic?

BEX5 p.Arg88Ser (c.264G>C) is classified Uncertain significance in BEX5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-14). AlphaMissense: likely pathogenic (0.924); Very rare (popmax 0.00156%, nfe).

How common is BEX5 p.Arg88Ser (c.264G>C) in the general population?

BEX5 p.Arg88Ser (c.264G>C) is very rare (popmax 0.00156%, nfe) (gnomAD).

What do computational predictors say about BEX5 p.Arg88Ser (c.264G>C)?

AlphaMissense predicts likely pathogenic (score 0.924) — an in-silico prediction, not a clinical call.

BEX5 p.Arg88Ser

c.264G>C · rs1416948596 · VCV3133767

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.924 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00156%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.924	likely pathogenic · top 9% in BEX5
REVEL	0.247	benign-leaning
SaProt	LLR -7.60	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.9	GERP -1.4
Regional constraint	o/e 1.11	unconstrained · MANE · 332 bp · p 0.3 · regional, not allelic
Overall
CADD	19.98	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 0.00156% European (non-Finnish) · 14/895,185 alleles

Filtering AF 0.000907% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00071%

Overall 0.00137% 15/1,098,077 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0021%	47,626
European (non-Finnish)grpmax	0.00156%	63,942

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: BEX5
Protein: p.Arg88Ser
Coding: c.264G>C
MANE Select: NM_001012978
dbSNP: rs1416948596
Type: single nucleotide variant
Location: chrX:102154002 (GRCh38)
Structure: AlphaFold pLDDT 64.96

Full BEX5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BEX5 p.Arg70Gln Uncertain significance ★ ⚠ same type
BEX5 p.Arg92Cys Uncertain significance ★ ⚠ same type
BEX5 p.Asn52Ile Uncertain significance ★ ⚠ same type
BEX5 p.Asp56Gly Uncertain significance ★ ⚠ same type
BEX5 p.Glu48Asp Uncertain significance ★ ⚠ same type
BEX5 p.Gly47Glu Uncertain significance ★ ⚠ same type
BEX5 p.Gly63Arg Uncertain significance ★ ⚠ same type
BEX5 p.His101Pro 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/bex5-p-arg88ser (accessed [today's date]).

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