Is EID2B p.Gln84Arg (c.251A>G) pathogenic?

EID2B p.Gln84Arg (c.251A>G) is classified Uncertain significance in EID2B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-18). AlphaMissense: likely benign (0.1289); Very rare (popmax 0.00568%, nfe).

How common is EID2B p.Gln84Arg (c.251A>G) in the general population?

EID2B p.Gln84Arg (c.251A>G) is very rare (popmax 0.00568%, nfe) (gnomAD).

What do computational predictors say about EID2B p.Gln84Arg (c.251A>G)?

AlphaMissense predicts likely benign (score 0.1289) — an in-silico prediction, not a clinical call.

EID2B p.Gln84Arg

c.251A>G · rs757988349 · VCV2327578

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1289 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00568%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1289	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -6.59	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 1.5	GERP -6.4, phastCons 0.96
Regional constraint	o/e 1.03	unconstrained · MANE · 482 bp · p 0.69 · regional, not allelic
Overall
CADD	8.318	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 0.00568% European (non-Finnish) · 67/1,179,980 alleles

Filtering AF 0.00453% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00417%

Overall 0.00428% 69/1,613,808 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00568%	17,612
Remaining individualsnot grpmax-eligible	0.0032%	31,238

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: EID2B
Protein: p.Gln84Arg
Coding: c.251A>G
MANE Select: NM_152361
dbSNP: rs757988349
Type: single nucleotide variant
Location: chr19:39532552 (GRCh38)
Gene constraint: LOEUF 1.759 · pLI 0.24 (gnomAD)
Structure: AlphaFold pLDDT 70.26

Full EID2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EID2B p.Ala131Val Uncertain significance ★ ⚠ same type
EID2B p.Ala134Thr Uncertain significance ★ ⚠ same type
EID2B p.Ala143Ser Uncertain significance ★ ⚠ same type
EID2B p.Ala45Thr Uncertain significance ★ ⚠ same type
EID2B p.Ala45Val Uncertain significance ★ ⚠ same type
EID2B p.Arg119Lys Uncertain significance ★ ⚠ same type
EID2B p.Gln83Pro Uncertain significance ★ ⚠ same type
EID2B p.Glu123Val 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/eid2b-p-gln84arg (accessed [today's date]).

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