Is EBP p.Leu85Ile (c.253C>A) pathogenic?

EBP p.Leu85Ile (c.253C>A) is classified Uncertain significance in EBP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-17). AlphaMissense: likely benign (0.085); Absent from gnomAD v4.1.

How common is EBP p.Leu85Ile (c.253C>A) in the general population?

EBP p.Leu85Ile (c.253C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EBP p.Leu85Ile (c.253C>A)?

AlphaMissense predicts likely benign (score 0.085) — an in-silico prediction, not a clinical call.

EBP p.Leu85Ile

c.253C>A · rs2147154732 · VCV1494536

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.085 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.085	likely benign
REVEL	0.257	benign-leaning
SaProt	LLR -7.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.83	GERP -0.021
Overall
CADD	14.4	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

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.Leu85Ile
Coding: c.253C>A
MANE Select: NM_001378122 · reported on NM_006579
dbSNP: rs2147154732
Type: single nucleotide variant
Location: chrX:48524024 (GRCh38)
Structure: AlphaFold pLDDT 59.09
Residue 85: the 'disordered' region

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

Similar variants

EBP p.Leu85fs Pathogenic ★ same residue
EBP p.Arg110Gln Pathogenic/Likely pathogenic ★★ same type
EBP p.Arg110Ter Pathogenic ★★ same type
EBP p.Arg147Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
EBP p.Arg147His Pathogenic ★★ ⚠ same type
EBP p.Arg62Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
EBP p.Glu80Lys Pathogenic/Likely pathogenic ★★ same type
EBP p.Gly161Arg Likely pathogenic ★★ same type

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-leu85ile (accessed [today's date]).

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