Is EBP p.Trp47Arg (c.139T>C) pathogenic?

EBP p.Trp47Arg (c.139T>C) is classified Pathogenic in EBP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2014-04-01). AlphaMissense: likely pathogenic (0.9132); Absent from gnomAD v4.1; Associated with MEND syndrome.

What condition is associated with EBP p.Trp47Arg (c.139T>C)?

EBP p.Trp47Arg (c.139T>C) is associated with MEND syndrome (ClinVar).

How common is EBP p.Trp47Arg (c.139T>C) in the general population?

EBP p.Trp47Arg (c.139T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EBP p.Trp47Arg (c.139T>C)?

AlphaMissense predicts likely pathogenic (score 0.9132) — an in-silico prediction, not a clinical call.

EBP p.Trp47Arg

c.139T>C · rs878854359 · VCV209040

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9132 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MEND syndrome

Computational evidence

Protein change
AlphaMissense	0.9132	likely pathogenic ✓ concordant with ClinVar · top 4% in EBP
REVEL	0.88	moderately pathogenic-leaning
SaProt	LLR -12.76	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.1	GERP 2, phastCons 1
Overall
CADD	24.8	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: EBP
Protein: p.Trp47Arg
Coding: c.139T>C
MANE Select: NM_006579
dbSNP: rs878854359
Type: single nucleotide variant
Location: chrX:48523910 (GRCh38)
Structure: AlphaFold pLDDT 59.09
Residue 47: the 'disordered' region

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

Disease context

MEND syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EBP p.Trp47Cys Pathogenic ★ same residue
EBP p.Trp47Ter Pathogenic ★ same residue
EBP p.Arg147Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
EBP p.Arg147His Pathogenic ★★ ⚠ same condition
EBP p.Ala95Thr Uncertain significance ★★ ⚠ same condition
EBP p.Arg62Gln Uncertain significance ★★ ⚠ same condition
EBP p.Asn116Ser Uncertain significance ★★ ⚠ same condition
EBP p.Trp186Arg Uncertain significance ★★ ⚠ same condition

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/ebp-p-trp47arg (accessed [today's date]).

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