Is EBP p.Leu18Pro (c.53T>C) pathogenic?

EBP p.Leu18Pro (c.53T>C) is classified Pathogenic in EBP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2003-10-15). AlphaMissense: ambiguous (0.56); Absent from gnomAD v4.1; Associated with MEND syndrome.

What condition is associated with EBP p.Leu18Pro (c.53T>C)?

EBP p.Leu18Pro (c.53T>C) is associated with MEND syndrome (ClinVar).

How common is EBP p.Leu18Pro (c.53T>C) in the general population?

EBP p.Leu18Pro (c.53T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EBP p.Leu18Pro (c.53T>C)?

AlphaMissense predicts ambiguous (score 0.56) — an in-silico prediction, not a clinical call.

EBP p.Leu18Pro

c.53T>C · rs104894795 · VCV11493

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.56 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

MEND syndrome

Computational evidence

Protein change
AlphaMissense	0.56	ambiguous
REVEL	0.903	moderately pathogenic-leaning
SaProt	LLR -10.50	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Overall
CADD	24.9	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.Leu18Pro
Coding: c.53T>C
MANE Select: NM_001378122 · reported on NM_006579
dbSNP: rs104894795
Type: single nucleotide variant
Location: chrX:48523824 (GRCh38)
Structure: AlphaFold pLDDT 59.09

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.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
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-leu18pro (accessed [today's date]).

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