Is BEX4 p.Met87Thr (c.260T>C) pathogenic?

BEX4 p.Met87Thr (c.260T>C) is classified Uncertain significance in BEX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-12). AlphaMissense: likely pathogenic (0.5994); Absent from gnomAD v4.1.

How common is BEX4 p.Met87Thr (c.260T>C) in the general population?

BEX4 p.Met87Thr (c.260T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BEX4 p.Met87Thr (c.260T>C)?

AlphaMissense predicts likely pathogenic (score 0.5994) — an in-silico prediction, not a clinical call.

BEX4 p.Met87Thr

c.260T>C · rs2520840431 · VCV2611202

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5994 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5994	likely pathogenic
REVEL	0.109	moderately benign-leaning
SaProt	LLR -8.31	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.001	GERP 0.68
Regional constraint	o/e 1.14	unconstrained · MANE · 359 bp · p 0.17 · regional, not allelic
Overall
CADD	16.56	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BEX4
Protein: p.Met87Thr
Coding: c.260T>C
MANE Select: NM_001080425
dbSNP: rs2520840431
Type: single nucleotide variant
Location: chrX:103216413 (GRCh38)
Structure: AlphaFold pLDDT 64.35
Residue 87: the 'interaction with alpha-tubulin' region; the 'interaction with sirt2' 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-met87thr (accessed [today's date]).

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