Is EBF2 p.Arg308Gln (c.923G>A) pathogenic?

EBF2 p.Arg308Gln (c.923G>A) is classified Uncertain significance in EBF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-26). AlphaMissense: likely pathogenic (0.9314); Very rare (popmax 0.00223%, eas).

How common is EBF2 p.Arg308Gln (c.923G>A) in the general population?

EBF2 p.Arg308Gln (c.923G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about EBF2 p.Arg308Gln (c.923G>A)?

AlphaMissense predicts likely pathogenic (score 0.9314) — an in-silico prediction, not a clinical call.

EBF2 p.Arg308Gln

c.923G>A · VCV3843239

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9314 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9314	likely pathogenic
REVEL	0.383	indeterminate
SaProt	LLR -14.47	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 178 kb · p 2.1e-08 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00223% East Asian · 1/44,852 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000685% 10/1,460,918 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,852
European (non-Finnish)	0.000763%	131,057

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: EBF2
Protein: p.Arg308Gln
Coding: c.923G>A
MANE Select: NM_022659
Type: single nucleotide variant
Location: chr8:25886841 (GRCh38)
Gene constraint: LOEUF 0.394 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.38
Residue 308: the ipt/tig domain

Full EBF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EBF2 c.1164+4A>G Benign ★★ same type
EBF2 p.Lys352= Benign ★★ same type
EBF2 p.Ala420Thr Uncertain significance ★ ⚠ same type
EBF2 p.Ala47Gly Uncertain significance ★ ⚠ same type
EBF2 p.Ala47Ser Uncertain significance ★ ⚠ same type
EBF2 p.Ala555Thr Uncertain significance ★ ⚠ same type
EBF2 p.Ala87Thr Uncertain significance ★ ⚠ same type
EBF2 p.Arg128Ser 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/ebf2-p-arg308gln (accessed [today's date]).

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