Is EBF4 p.Val72Met (c.214G>A) pathogenic?

EBF4 p.Val72Met (c.214G>A) is classified Uncertain significance in EBF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-10). AlphaMissense: likely pathogenic (0.9928); Ultra-rare (popmax 0.0166%, mid).

How common is EBF4 p.Val72Met (c.214G>A) in the general population?

EBF4 p.Val72Met (c.214G>A) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about EBF4 p.Val72Met (c.214G>A)?

AlphaMissense predicts likely pathogenic (score 0.9928) — an in-silico prediction, not a clinical call.

EBF4 p.Val72Met

c.214G>A · rs1202921729 · VCV3086847

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9928 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9928	likely pathogenic
REVEL	0.364	indeterminate
SaProt	LLR -13.35	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL 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

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 0.0166% Middle Eastern · 1/6,016 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00106%

Overall 0.000901% 14/1,553,092 alleles · ultra-rare exomes 9/1,401,012 · genomes 5/152,080 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,016
African / African-American	0.00547%	18,296
Remaining individualsnot grpmax-eligible	0.00498%	20,069
East Asian	0.00485%	20,627
South Asian	0.00238%	42,059
European (non-Finnish)	0.000174%	573,849

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.Val72Met
Coding: c.214G>A
MANE Select: NM_001395167
dbSNP: rs1202921729
Type: single nucleotide variant
Location: chr20:2705653 (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.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
EBF4 p.Ala522Val 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-val72met (accessed [today's date]).

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