Is BEX5 p.His101Pro (c.302A>C) pathogenic?

BEX5 p.His101Pro (c.302A>C) is classified Uncertain significance in BEX5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-21). AlphaMissense: ambiguous (0.428); Very rare (popmax 0.00174%, afr).

How common is BEX5 p.His101Pro (c.302A>C) in the general population?

BEX5 p.His101Pro (c.302A>C) is very rare (popmax 0.00174%, afr) (gnomAD).

What do computational predictors say about BEX5 p.His101Pro (c.302A>C)?

AlphaMissense predicts ambiguous (score 0.428) — an in-silico prediction, not a clinical call.

BEX5 p.His101Pro

c.302A>C · VCV3480511

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.428 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00174%, afr)

Computational evidence

Protein change
AlphaMissense	0.428	ambiguous
REVEL	0.296	indeterminate
SaProt	LLR -6.79	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.41	GERP 1.9
Regional constraint	o/e 1.11	unconstrained · MANE · 332 bp · p 0.3 · regional, not allelic
Overall
CADD	21.5	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 0.00174% African / African-American · 1/57,476 alleles

Overall 9.12e-05% 1/1,096,719 alleles · very rare

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.His101Pro
Coding: c.302A>C
MANE Select: NM_001012978
Type: single nucleotide variant
Location: chrX:102153964 (GRCh38)
Structure: AlphaFold pLDDT 64.96
Residue 101: the 'his cluster' region

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.Arg88Ser 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

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-his101pro (accessed [today's date]).

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