Is EBF2 p.Asn219Ile (c.656A>T) pathogenic?

EBF2 p.Asn219Ile (c.656A>T) is classified Uncertain significance in EBF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: ambiguous (0.3462); Absent from gnomAD v4.1.

How common is EBF2 p.Asn219Ile (c.656A>T) in the general population?

EBF2 p.Asn219Ile (c.656A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EBF2 p.Asn219Ile (c.656A>T)?

AlphaMissense predicts ambiguous (score 0.3462) — an in-silico prediction, not a clinical call.

EBF2 p.Asn219Ile

c.656A>T · VCV4246234

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3462 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3462	ambiguous
REVEL	0.112	moderately benign-leaning
SaProt	LLR -11.75	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 0.79, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 178 kb · p 2.1e-08 · regional, not allelic
Overall
CADD	23.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EBF2
Protein: p.Asn219Ile
Coding: c.656A>T
MANE Select: NM_022659
Type: single nucleotide variant
Location: chr8:25889847 (GRCh38)
Gene constraint: LOEUF 0.394 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.38

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-asn219ile (accessed [today's date]).

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