Is BEX4 p.Ser3Phe (c.8C>T) pathogenic?

BEX4 p.Ser3Phe (c.8C>T) is classified Uncertain significance in BEX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely benign (0.3123); Very rare (popmax 0.00557%, afr).

How common is BEX4 p.Ser3Phe (c.8C>T) in the general population?

BEX4 p.Ser3Phe (c.8C>T) is very rare (popmax 0.00557%, afr) (gnomAD).

What do computational predictors say about BEX4 p.Ser3Phe (c.8C>T)?

AlphaMissense predicts likely benign (score 0.3123) — an in-silico prediction, not a clinical call.

BEX4 p.Ser3Phe

c.8C>T · rs2520838526 · VCV3133764

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3123 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00557%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3123	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -8.50	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 0.072	GERP 0.98, phastCons 0.1
Regional constraint	o/e 1.14	unconstrained · MANE · 359 bp · p 0.17 · regional, not allelic
Overall
CADD	20.3	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 0.00557% African / African-American · 3/53,837 alleles

Filtering AF 0.00148% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00071%

Overall 0.000351% 4/1,139,726 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00557%	17,946
Remaining individualsnot grpmax-eligible	0.00224%	44,551

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.Ser3Phe
Coding: c.8C>T
MANE Select: NM_001080425
dbSNP: rs2520838526
Type: single nucleotide variant
Location: chrX:103216161 (GRCh38)
Structure: AlphaFold pLDDT 64.35
Residue 3: the 'disordered' 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-ser3phe (accessed [today's date]).

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