Is EBP p.Cys127Ser (c.380G>C) pathogenic?

EBP p.Cys127Ser (c.380G>C) is classified Uncertain significance in EBP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: likely benign (0.1687); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with EBP p.Cys127Ser (c.380G>C)?

EBP p.Cys127Ser (c.380G>C) is associated with Inborn genetic diseases (ClinVar).

How common is EBP p.Cys127Ser (c.380G>C) in the general population?

EBP p.Cys127Ser (c.380G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EBP p.Cys127Ser (c.380G>C)?

AlphaMissense predicts likely benign (score 0.1687) — an in-silico prediction, not a clinical call.

EBP p.Cys127Ser

c.380G>C · VCV4015966

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1687 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1687	likely benign
REVEL	0.289	benign-leaning
SaProt	LLR -5.36	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 -0.42	GERP -4.2
Overall
CADD	1.598	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.Cys127Ser
Coding: c.380G>C
MANE Select: NM_001378122 · reported on NM_006579
Type: single nucleotide variant
Location: chrX:48527196 (GRCh38)
Structure: AlphaFold pLDDT 59.09
Residue 127: 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.Cys127Ter Pathogenic ★ 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-cys127ser (accessed [today's date]).

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