Is EBF3 p.Ile401Phe (c.1201A>T) pathogenic?

EBF3 p.Ile401Phe (c.1201A>T) is classified Uncertain significance in EBF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-10). AlphaMissense: likely pathogenic (0.8951); Absent from gnomAD v4.1.

How common is EBF3 p.Ile401Phe (c.1201A>T) in the general population?

EBF3 p.Ile401Phe (c.1201A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EBF3 p.Ile401Phe (c.1201A>T)?

AlphaMissense predicts likely pathogenic (score 0.8951) — an in-silico prediction, not a clinical call.

EBF3 p.Ile401Phe

c.1201A>T · VCV3572835

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8951 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8951	likely pathogenic
REVEL	0.151	moderately benign-leaning
SaProt	LLR -7.46	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.1	GERP 2.6, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 10 kb · p 1.1e-05 · regional, not allelic
Overall
CADD	25.7	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: EBF3
Protein: p.Ile401Phe
Coding: c.1201A>T
MANE Select: NM_001375380
Type: single nucleotide variant
Location: chr10:129842287 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.89 · 2 PDB
Residue 401: an α-helix

Full EBF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EBF3 c.486-1G>A Pathogenic ★★ same type
EBF3 c.555-2A>G Likely pathogenic ★★ same type
EBF3 p.Arg152Gly Pathogenic ★★ same type
EBF3 p.Arg163Gln Pathogenic ★★ same type
EBF3 p.Arg163Leu Pathogenic ★★ same type
EBF3 p.Arg163Trp Pathogenic/Likely pathogenic ★★ same type
EBF3 p.Arg206Ter Pathogenic ★★ same type
EBF3 p.Arg209Gln Pathogenic/Likely pathogenic ★★ 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/ebf3-p-ile401phe (accessed [today's date]).

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