Is BEX4 p.Phe105Val (c.313T>G) pathogenic?

BEX4 p.Phe105Val (c.313T>G) is classified Uncertain significance in BEX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-25). AlphaMissense: ambiguous (0.4774); Very rare (popmax 0.000447%, nfe).

How common is BEX4 p.Phe105Val (c.313T>G) in the general population?

BEX4 p.Phe105Val (c.313T>G) is very rare (popmax 0.000447%, nfe) (gnomAD).

What do computational predictors say about BEX4 p.Phe105Val (c.313T>G)?

AlphaMissense predicts ambiguous (score 0.4774) — an in-silico prediction, not a clinical call.

BEX4 p.Phe105Val

c.313T>G · VCV3480509

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4774 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000447%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4774	ambiguous
REVEL	0.085	moderately benign-leaning
SaProt	LLR -5.61	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 -4.3	GERP -3.2
Regional constraint	o/e 1.14	unconstrained · MANE · 359 bp · p 0.17 · regional, not allelic
Overall
CADD	14.82	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 0.000447% European (non-Finnish) · 4/895,056 alleles

Filtering AF 0.000105% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.1e-05%

Overall 0.000331% 4/1,209,544 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: BEX4
Protein: p.Phe105Val
Coding: c.313T>G
MANE Select: NM_001080425
Type: single nucleotide variant
Location: chrX:103216466 (GRCh38)
Structure: AlphaFold pLDDT 64.35
Residue 105: the 'interaction with alpha-tubulin' 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.Asn11Ser 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-phe105val (accessed [today's date]).

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