Is EBP p.Gly173Arg (c.517G>A) pathogenic?

EBP p.Gly173Arg (c.517G>A) is classified Uncertain significance in EBP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-25). AlphaMissense: likely benign (0.2852); Ultra-rare (popmax 0.046%, mid); Associated with Inborn genetic diseases.

What condition is associated with EBP p.Gly173Arg (c.517G>A)?

EBP p.Gly173Arg (c.517G>A) is associated with Inborn genetic diseases (ClinVar).

How common is EBP p.Gly173Arg (c.517G>A) in the general population?

EBP p.Gly173Arg (c.517G>A) is ultra-rare (popmax 0.046%, mid) (gnomAD).

What do computational predictors say about EBP p.Gly173Arg (c.517G>A)?

AlphaMissense predicts likely benign (score 0.2852) — an in-silico prediction, not a clinical call.

EBP p.Gly173Arg

c.517G>A · rs781964042 · VCV1684701

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2852 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.046%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2852	likely benign
REVEL	0.945	strongly pathogenic-leaning
SaProt	LLR -10.47	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 2.1, phastCons 1
Overall
CADD	25.7	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

Grpmax group 0.046% Middle Eastern · 2/4,352 alleles

Filtering AF 0.00822% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00616%

Overall 0.00146% 16/1,098,004 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.046%	2,176
South Asian	0.0158%	6,322
Remaining individualsnot grpmax-eligible	0.0021%	47,642
European (non-Finnish)	0.000447%	223,870

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.Gly173Arg
Coding: c.517G>A
MANE Select: NM_001378122 · reported on NM_006579
dbSNP: rs781964042
Type: single nucleotide variant
Location: chrX:48528281 (GRCh38)
Structure: AlphaFold pLDDT 59.09
Residue 173: 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.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
EBP p.Cys127Ser Uncertain significance ★ ⚠ same condition
EBP p.Gln143Arg Conflicting classifications of pathogenicity ★ ⚠ 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-gly173arg (accessed [today's date]).

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