Is BEX1 p.Leu70Phe (c.208C>T) pathogenic?

BEX1 p.Leu70Phe (c.208C>T) is classified Uncertain significance in BEX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-26). AlphaMissense: likely benign (0.1148); Very rare (popmax 9.11e-05%).

How common is BEX1 p.Leu70Phe (c.208C>T) in the general population?

BEX1 p.Leu70Phe (c.208C>T) is very rare (popmax 9.11e-05%) (gnomAD).

What do computational predictors say about BEX1 p.Leu70Phe (c.208C>T)?

AlphaMissense predicts likely benign (score 0.1148) — an in-silico prediction, not a clinical call.

BEX1 p.Leu70Phe

c.208C>T · rs2520444041 · VCV2273403

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1148 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 9.11e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1148	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -6.88	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 2.8	GERP -0.072, phastCons 0.48
Regional constraint	o/e 1.13	unconstrained · MANE · 237 bp · p 0.29 · regional, not allelic
Overall
CADD	19.27	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 9.11e-05%

Overall 9.11e-05% 1/1,098,266 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: BEX1
Protein: p.Leu70Phe
Coding: c.208C>T
MANE Select: NM_018476
dbSNP: rs2520444041
Type: single nucleotide variant
Location: chrX:103063067 (GRCh38)
Structure: AlphaFold pLDDT 68.10

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

Similar variants

BEX1 p.Leu70Pro Uncertain significance ★ ⚠ same residue
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

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-leu70phe (accessed [today's date]).

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