Is EBP p.Glu88Lys (c.262G>A) pathogenic?

EBP p.Glu88Lys (c.262G>A) is classified Uncertain significance in EBP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-04). AlphaMissense: likely benign (0.0619); Ultra-rare (popmax 0.0229%, mid); Associated with Inborn genetic diseases.

What condition is associated with EBP p.Glu88Lys (c.262G>A)?

EBP p.Glu88Lys (c.262G>A) is associated with Inborn genetic diseases (ClinVar).

How common is EBP p.Glu88Lys (c.262G>A) in the general population?

EBP p.Glu88Lys (c.262G>A) is ultra-rare (popmax 0.0229%, mid) (gnomAD).

What do computational predictors say about EBP p.Glu88Lys (c.262G>A)?

AlphaMissense predicts likely benign (score 0.0619) — an in-silico prediction, not a clinical call.

EBP p.Glu88Lys

c.262G>A · VCV3506398

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0619 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0229%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0619	likely benign
REVEL	0.543	indeterminate
SaProt	LLR -3.29	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.69	GERP -4.1, phastCons 0.006
Overall
CADD	8.824	PHRED · no single calibrated threshold — expert panels disagree

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

Grpmax group 0.0229% Middle Eastern · 1/4,372 alleles

Filtering AF 0.000584% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000219%

Overall 0.000661% 8/1,209,559 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0229%	4,372
Ashkenazi Jewishnot grpmax-eligible	0.00454%	22,025
South Asian	0.00352%	28,403
European (non-Finnish)	0.000447%	223,796

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: EBP
Protein: p.Glu88Lys
Coding: c.262G>A
MANE Select: NM_001378122 · reported on NM_006579
Type: single nucleotide variant
Location: chrX:48524033 (GRCh38)
Structure: AlphaFold pLDDT 59.09
Residue 88: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EBP p.Glu88Gln Likely benign ★ same residue
EBP p.Gly173Arg Uncertain significance ★★ ⚠ same condition
EBP p.Gly177Arg Uncertain significance ★★ ⚠ same condition
EBP p.Arg171His Benign/Likely benign ★★ ⚠ same condition
EBP p.Arg52Cys Benign/Likely benign ★★ ⚠ same condition
EBP c.301+3G>C Conflicting classifications of pathogenicity ★ same condition
EBP p.Arg142His Uncertain significance ★ ⚠ same condition
EBP p.Asn4Ile 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-glu88lys (accessed [today's date]).

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