Is EBP p.Ile75Asn (c.224T>A) pathogenic?

EBP p.Ile75Asn (c.224T>A) is classified Likely pathogenic in EBP (ClinVar, Single submitter, 2 submitters; last evaluated 2025-02-27). AlphaMissense: likely pathogenic (0.7723); Absent from gnomAD v4.1; Associated with MEND syndrome.

What condition is associated with EBP p.Ile75Asn (c.224T>A)?

EBP p.Ile75Asn (c.224T>A) is associated with MEND syndrome (ClinVar).

How common is EBP p.Ile75Asn (c.224T>A) in the general population?

EBP p.Ile75Asn (c.224T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EBP p.Ile75Asn (c.224T>A)?

AlphaMissense predicts likely pathogenic (score 0.7723) — an in-silico prediction, not a clinical call.

EBP p.Ile75Asn

c.224T>A · rs797045153 · VCV209039

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7723 · 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	0.7723	likely pathogenic ✓ concordant with ClinVar · top 8% in EBP
REVEL	0.892	moderately pathogenic-leaning
SaProt	LLR -13.17	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, phastCons 1
Overall
CADD	26.6	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.Ile75Asn
Coding: c.224T>A
MANE Select: NM_001378122 · reported on NM_006579
dbSNP: rs797045153
Type: single nucleotide variant
Location: chrX:48523995 (GRCh38)
Structure: AlphaFold pLDDT 59.09
Residue 75: 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.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-ile75asn (accessed [today's date]).

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