Is EBF4 p.Arg78Gln (c.233G>A) pathogenic?

EBF4 p.Arg78Gln (c.233G>A) is classified Uncertain significance in EBF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-15). AlphaMissense: ambiguous (0.3707); Ultra-rare (popmax 0.0122%, eas).

How common is EBF4 p.Arg78Gln (c.233G>A) in the general population?

EBF4 p.Arg78Gln (c.233G>A) is ultra-rare (popmax 0.0122%, eas) (gnomAD).

What do computational predictors say about EBF4 p.Arg78Gln (c.233G>A)?

AlphaMissense predicts ambiguous (score 0.3707) — an in-silico prediction, not a clinical call.

EBF4 p.Arg78Gln

c.233G>A · rs766860031 · VCV2207863

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3707 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0122%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3707	ambiguous
REVEL	0.226	benign-leaning
SaProt	LLR -10.19	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 44 kb · p 4.3e-06 · regional, not allelic
Overall
CADD	33.0	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 0.0122% East Asian · 5/40,972 alleles

Filtering AF 0.00478% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00308%

Overall 0.0018% 28/1,551,848 alleles · ultra-rare exomes 26/1,399,810 · genomes 2/152,038 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0122%	8,194
Admixed American	0.00196%	50,980
European (non-Finnish)	0.00174%	57,357
African / African-American	0.00137%	73,068
South Asian	0.00119%	84,076

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: EBF4
Protein: p.Arg78Gln
Coding: c.233G>A
MANE Select: NM_001395167
dbSNP: rs766860031
Type: single nucleotide variant
Location: chr20:2705672 (GRCh38)
Gene constraint: LOEUF 0.868 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.60

Full EBF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EBF4 p.Arg78Trp Uncertain significance ★ ⚠ same residue
EBF4 p.Arg164= Benign ★★ same type
EBF4 p.Ile91= Benign ★★ same type
EBF4 p.Ala102Thr Uncertain significance ★ ⚠ same type
EBF4 p.Ala102Val Uncertain significance ★ ⚠ same type
EBF4 p.Ala402Thr Uncertain significance ★ ⚠ same type
EBF4 p.Ala40Thr Uncertain significance ★ ⚠ same type
EBF4 p.Ala438Ser 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/ebf4-p-arg78gln (accessed [today's date]).

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