Is BEX1 p.Pro58Ser (c.172C>T) pathogenic?

BEX1 p.Pro58Ser (c.172C>T) is classified Uncertain significance in BEX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-12). AlphaMissense: ambiguous (0.5067); Very rare (popmax 0.00176%, sas).

How common is BEX1 p.Pro58Ser (c.172C>T) in the general population?

BEX1 p.Pro58Ser (c.172C>T) is very rare (popmax 0.00176%, sas) (gnomAD).

What do computational predictors say about BEX1 p.Pro58Ser (c.172C>T)?

AlphaMissense predicts ambiguous (score 0.5067) — an in-silico prediction, not a clinical call.

BEX1 p.Pro58Ser

c.172C>T · VCV3480507

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5067 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00176%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5067	ambiguous
REVEL	0.087	moderately benign-leaning
SaProt	LLR -5.39	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 1.9, phastCons 0.29
Regional constraint	o/e 1.13	unconstrained · MANE · 237 bp · p 0.29 · regional, not allelic
Overall
CADD	18.04	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 0.00176% South Asian · 1/56,965 alleles

Filtering AF 0.000164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000119%

Overall 0.000546% 6/1,098,259 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00176%	56,965
European (non-Finnish)	0.000558%	179,106

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: BEX1
Protein: p.Pro58Ser
Coding: c.172C>T
MANE Select: NM_018476
Type: single nucleotide variant
Location: chrX:103063103 (GRCh38)
Structure: AlphaFold pLDDT 68.10

Full BEX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BEX1 p.Ala17Asp Uncertain significance ★ ⚠ same type
BEX1 p.Ala35Val Conflicting classifications of pathogenicity ★ ⚠ same type
BEX1 p.Arg106Trp Uncertain significance ★ ⚠ same type
BEX1 p.Arg50His Uncertain significance ★ ⚠ same type
BEX1 p.Arg54Cys Uncertain significance ★ ⚠ same type
BEX1 p.Arg54His Uncertain significance ★ ⚠ same type
BEX1 p.Arg84Lys Uncertain significance ★ ⚠ same type
BEX1 p.Asn10Asp 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/bex1-p-pro58ser (accessed [today's date]).

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