Is EBF4 p.Val491Ala (c.1472T>C) pathogenic?

EBF4 p.Val491Ala (c.1472T>C) is classified Uncertain significance in EBF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-15). AlphaMissense: likely benign (0.1143); No allele count reported in gnomAD v4.1 (AN 1,264,784).

How common is EBF4 p.Val491Ala (c.1472T>C) in the general population?

EBF4 p.Val491Ala (c.1472T>C) is no allele count reported in gnomAD v4.1 (AN 1,264,784) (gnomAD).

What do computational predictors say about EBF4 p.Val491Ala (c.1472T>C)?

AlphaMissense predicts likely benign (score 0.1143) — an in-silico prediction, not a clinical call.

EBF4 p.Val491Ala

c.1472T>C · rs2514914276 · VCV2619236

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1143 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,264,784)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1143	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -5.02	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 9,329 bp · p 0.2 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

No allele count reported in gnomAD v4.1 (AN 1,264,784). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EBF4
Protein: p.Val491Ala
Coding: c.1472T>C
MANE Select: NM_001395167
dbSNP: rs2514914276
Type: single nucleotide variant
Location: chr20:2752477 (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-val491ala (accessed [today's date]).

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