Is EBP p.Trp186Arg (c.556T>C) pathogenic?

EBP p.Trp186Arg (c.556T>C) is classified Uncertain significance in EBP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-12-28). AlphaMissense: likely pathogenic (0.9286); Absent from gnomAD v4.1; Associated with MEND syndrome.

What condition is associated with EBP p.Trp186Arg (c.556T>C)?

EBP p.Trp186Arg (c.556T>C) is associated with MEND syndrome (ClinVar).

How common is EBP p.Trp186Arg (c.556T>C) in the general population?

EBP p.Trp186Arg (c.556T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EBP p.Trp186Arg (c.556T>C)?

AlphaMissense predicts likely pathogenic (score 0.9286) — an in-silico prediction, not a clinical call.

EBP p.Trp186Arg

c.556T>C · rs2147157059 · VCV1526120

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9286 · 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	0.9286	likely pathogenic · top 4% in EBP
REVEL	0.94	strongly pathogenic-leaning
SaProt	LLR -14.10	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.1, phastCons 1
Overall
CADD	28.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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.Trp186Arg
Coding: c.556T>C
MANE Select: NM_001378122 · reported on NM_006579
dbSNP: rs2147157059
Type: single nucleotide variant
Location: chrX:48528320 (GRCh38)
Structure: AlphaFold pLDDT 59.09
Residue 186: 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.Trp186Ter 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.Ala5Thr Benign/Likely benign ★★ same condition
EBP p.Thr217Met Benign/Likely benign ★★ 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-trp186arg (accessed [today's date]).

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