Is EBF2 p.Asn500Ser (c.1499A>G) pathogenic?

EBF2 p.Asn500Ser (c.1499A>G) is classified Uncertain significance in EBF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.0639); Very rare (popmax 0.000847%, nfe).

How common is EBF2 p.Asn500Ser (c.1499A>G) in the general population?

EBF2 p.Asn500Ser (c.1499A>G) is very rare (popmax 0.000847%, nfe) (gnomAD).

What do computational predictors say about EBF2 p.Asn500Ser (c.1499A>G)?

AlphaMissense predicts likely benign (score 0.0639) — an in-silico prediction, not a clinical call.

EBF2 p.Asn500Ser

c.1499A>G · VCV4662850

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0639 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000847%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0639	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -6.42	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 6.1	GERP 0.61, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 18 kb · p 0.58 · regional, not allelic
Overall
CADD	19.92	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

Grpmax group 0.000847% European (non-Finnish) · 10/1,180,002 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000684% 10/1,461,878 alleles · very rare

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: EBF2
Protein: p.Asn500Ser
Coding: c.1499A>G
MANE Select: NM_022659
Type: single nucleotide variant
Location: chr8:25858348 (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-asn500ser (accessed [today's date]).

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