Is EBI3 p.Arg73Gln (c.218G>A) pathogenic?

EBI3 p.Arg73Gln (c.218G>A) is classified Likely benign in EBI3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). AlphaMissense: likely benign (0.0668); Ultra-rare (popmax 0.0189%, nfe).

How common is EBI3 p.Arg73Gln (c.218G>A) in the general population?

EBI3 p.Arg73Gln (c.218G>A) is ultra-rare (popmax 0.0189%, nfe) (gnomAD).

What do computational predictors say about EBI3 p.Arg73Gln (c.218G>A)?

AlphaMissense predicts likely benign (score 0.0668) — an in-silico prediction, not a clinical call.

EBI3 p.Arg73Gln

c.218G>A · rs147339690 · VCV2463969

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0668 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0189%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0668	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -5.95	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 -1.1	GERP -2.9
Regional constraint	o/e 1.05	unconstrained · MANE · 7,534 bp · p 0.34 · regional, not allelic
Overall
CADD	3.411	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 0.0189% European (non-Finnish) · 223/1,177,240 alleles

Filtering AF 0.0169% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0161%

Overall 0.0151% 241/1,596,978 alleles · ultra-rare exomes 223/1,444,702 · genomes 18/152,276 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0189%	5,279
Remaining individualsnot grpmax-eligible	0.0145%	6,889
African / African-American	0.00668%	14,980
South Asian	0.00222%	45,071
Finnishnot grpmax-eligible	0.00187%	53,404
Admixed American	0.00169%	59,264

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: EBI3
Protein: p.Arg73Gln
Coding: c.218G>A
MANE Select: NM_005755
dbSNP: rs147339690
Type: single nucleotide variant
Location: chr19:4233146 (GRCh38)
Gene constraint: LOEUF 1.373 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.34 · 4 PDB
Residue 73: a β-strand; the fibronectin type-iii 1 domain

Full EBI3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EBI3 p.Arg73Trp Uncertain significance ★ ⚠ same residue
EBI3 c.200+3C>T Benign ★★ same type
EBI3 p.Ala13Thr Uncertain significance ★ ⚠ same type
EBI3 p.Ala205Ser Uncertain significance ★ ⚠ same type
EBI3 p.Ala27Val Uncertain significance ★ ⚠ same type
EBI3 p.Arg136Cys Uncertain significance ★ ⚠ same type
EBI3 p.Arg136His Uncertain significance ★ ⚠ same type
EBI3 p.Arg143His Uncertain significance ★ ⚠ 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/ebi3-p-arg73gln (accessed [today's date]).

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